Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0008053 mitochondrial fusion	IBA GO_REF:0000033	ACCEPT	Summary: mitochondrial fusion (GO:0008053) is supported for opa1. Reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene. Supporting Evidence: file:DANRE/opa1/opa1-uniprot.txt mediating fusion of the mitochondrial inner membranes PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae file:DANRE/opa1/opa1-deep-research-falcon.md OPA1 mediates IMM fusion after MFN1/MFN2-dependent OMM fusion and also shapes/maintains cristae; GTP-dependent oligomerization/dimerization drives membrane curvature and fusion.
GO:0031966 mitochondrial membrane	IBA GO_REF:0000033	MARK AS OVER ANNOTATED	Summary: mitochondrial membrane (GO:0031966) is a broad parent of the more specific, also-accepted CC term GO:0005743 (mitochondrial inner membrane) and is therefore redundant for opa1. Reason: GO:0031966 (mitochondrial membrane) is an is_a ancestor of GO:0005743 (mitochondrial inner membrane), confirmed via OLS getAncestors. GO:0005743 is independently ACCEPTED on this review and is the correct specific localization for OPA1 (inner mitochondrial membrane), so the broader parent term is an over-annotation. Supporting Evidence: file:DANRE/opa1/opa1-deep-research-falcon.md OPA1 is localized to the inner mitochondrial membrane (IMM), where the long form is membrane-anchored and the short form is soluble in the intermembrane space.
GO:0016559 peroxisome fission	IBA GO_REF:0000033	REMOVE	Summary: peroxisome fission (GO:0016559) is the wrong organelle and wrong process direction for opa1 and should be removed. Reason: OPA1/opa1 is a mitochondrial inner-membrane dynamin-like GTPase that mediates membrane fusion, not fission, and has no known role in peroxisome biology. This IBA term is most plausibly a mis-transfer from other dynamin-superfamily members (e.g., DRP1/DNM1L) that do mediate peroxisome fission. It conflicts with the gene's established mitochondrial fusion function on both organelle and process-direction grounds. Supporting Evidence: file:DANRE/opa1/opa1-uniprot.txt mediating fusion of the mitochondrial inner membranes
GO:0005758 mitochondrial intermembrane space	IBA GO_REF:0000033	ACCEPT	Summary: mitochondrial intermembrane space (GO:0005758) is supported for opa1. Reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene. Supporting Evidence: file:DANRE/opa1/opa1-uniprot.txt mediating fusion of the mitochondrial inner membranes PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae file:DANRE/opa1/opa1-deep-research-falcon.md OPA1 is localized to the inner mitochondrial membrane (IMM), where the long form is membrane-anchored and the short form is soluble in the intermembrane space.
GO:0008017 microtubule binding	IBA GO_REF:0000033	UNDECIDED	Summary: microtubule binding (GO:0008017) is a phylogenetic IBA inference from dynamin-superfamily members with no zebrafish-specific support or refutation; the original supporting_text quoted inner-membrane-fusion evidence that does not bear on microtubule binding. Reason: This annotation is an IBA (GO_REF:0000033) phylogenetic transfer from the dynamin superfamily; no microtubule-binding evidence for zebrafish opa1 exists in the UniProt entry, the cited PMID:23516612, or the falcon deep research report, and none refutes it either. The previously cited supporting_text described mitochondrial inner-membrane fusion, which is unrelated to microtubule binding, so it has been removed. Marked UNDECIDED pending experimental evidence.
GO:0003924 GTPase activity	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: GTPase activity (GO:0003924) is a broad parent of the more specific, also-accepted MF term GO:0140523 (GTPase-dependent fusogenic activity) and is therefore redundant for opa1. Reason: GO:0003924 (GTPase activity) is an is_a ancestor of GO:0140523 (GTPase-dependent fusogenic activity), confirmed via OLS getAncestors. GO:0140523 is independently ACCEPTED and captures the gene's specific GTPase-driven membrane-fusion role, so the generic parent GTPase activity term is an over-annotation. Supporting Evidence: file:DANRE/opa1/opa1-deep-research-falcon.md its catalytic activity is GTP hydrolysis (GTP → GDP + Pi), coupled to conformational changes that power membrane remodeling, tethering, and fusion.
GO:0005525 GTP binding	IEA GO_REF:0000002	ACCEPT	Summary: GTP binding (GO:0005525) is supported for opa1. Reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene. Supporting Evidence: file:DANRE/opa1/opa1-uniprot.txt mediating fusion of the mitochondrial inner membranes PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
GO:0005743 mitochondrial inner membrane	IEA GO_REF:0000044	ACCEPT	Summary: mitochondrial inner membrane (GO:0005743) is supported for opa1. Reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene. Supporting Evidence: file:DANRE/opa1/opa1-uniprot.txt mediating fusion of the mitochondrial inner membranes PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae file:DANRE/opa1/opa1-deep-research-falcon.md OPA1 is localized to the inner mitochondrial membrane (IMM), where the long form is membrane-anchored and the short form is soluble in the intermembrane space.
GO:0005758 mitochondrial intermembrane space	IEA GO_REF:0000044	ACCEPT	Summary: mitochondrial intermembrane space (GO:0005758) is supported for opa1. Reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene. Supporting Evidence: file:DANRE/opa1/opa1-uniprot.txt mediating fusion of the mitochondrial inner membranes PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae file:DANRE/opa1/opa1-deep-research-falcon.md OPA1 is localized to the inner mitochondrial membrane (IMM), where the long form is membrane-anchored and the short form is soluble in the intermembrane space.
GO:0061025 membrane fusion	IEA GO_REF:0000108	ACCEPT	Summary: membrane fusion (GO:0061025) is supported for opa1. Reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene. Supporting Evidence: file:DANRE/opa1/opa1-uniprot.txt mediating fusion of the mitochondrial inner membranes PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae file:DANRE/opa1/opa1-deep-research-falcon.md OPA1 is a TRAFAC class dynamin-like GTPase that localizes to mitochondria and is essential for IMM fusion, acting after outer mitochondrial membrane (OMM) fusion mediated by mitofusins (MFN1/MFN2).
GO:0003924 GTPase activity	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: GTPase activity (GO:0003924) is a broad parent of the more specific, also-accepted MF term GO:0140523 (GTPase-dependent fusogenic activity) and is therefore redundant for opa1. Reason: GO:0003924 (GTPase activity) is an is_a ancestor of GO:0140523 (GTPase-dependent fusogenic activity), confirmed via OLS getAncestors. GO:0140523 is independently ACCEPTED and captures the gene's specific GTPase-driven membrane-fusion role, so the generic parent GTPase activity term is an over-annotation. (Same term id GO:0003924 as the IEA instance, handled consistently.) Supporting Evidence: file:DANRE/opa1/opa1-deep-research-falcon.md its catalytic activity is GTP hydrolysis (GTP → GDP + Pi), coupled to conformational changes that power membrane remodeling, tethering, and fusion.
GO:0005743 mitochondrial inner membrane	ISS GO_REF:0000024	ACCEPT	Summary: mitochondrial inner membrane (GO:0005743) is supported for opa1. Reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene. Supporting Evidence: file:DANRE/opa1/opa1-uniprot.txt mediating fusion of the mitochondrial inner membranes PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae file:DANRE/opa1/opa1-deep-research-falcon.md OPA1 is localized to the inner mitochondrial membrane (IMM), where the long form is membrane-anchored and the short form is soluble in the intermembrane space.
GO:0005758 mitochondrial intermembrane space	ISS GO_REF:0000024	ACCEPT	Summary: mitochondrial intermembrane space (GO:0005758) is supported for opa1. Reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene. Supporting Evidence: file:DANRE/opa1/opa1-uniprot.txt mediating fusion of the mitochondrial inner membranes PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae file:DANRE/opa1/opa1-deep-research-falcon.md OPA1 is localized to the inner mitochondrial membrane (IMM), where the long form is membrane-anchored and the short form is soluble in the intermembrane space.
GO:0032740 positive regulation of interleukin-17 production	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: positive regulation of interleukin-17 production (GO:0032740) likely overstates the direct function of opa1. Reason: Opa1 directly mediates mitochondrial inner membrane fusion and cristae organization; the Th17/IL-17 pathway term is a distant ISS transfer without zebrafish-specific support. Supporting Evidence: file:DANRE/opa1/opa1-uniprot.txt mediating fusion of the mitochondrial inner membranes PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
GO:2000330 positive regulation of T-helper 17 cell lineage commitment	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: positive regulation of T-helper 17 cell lineage commitment (GO:2000330) likely overstates the direct function of opa1. Reason: Opa1 directly mediates mitochondrial inner membrane fusion and cristae organization; the Th17/IL-17 pathway term is a distant ISS transfer without zebrafish-specific support. Supporting Evidence: file:DANRE/opa1/opa1-uniprot.txt mediating fusion of the mitochondrial inner membranes PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
GO:0097749 membrane tubulation	ISS GO_REF:0000024	ACCEPT	Summary: membrane tubulation (GO:0097749) is supported for opa1. Reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene. Supporting Evidence: file:DANRE/opa1/opa1-uniprot.txt mediating fusion of the mitochondrial inner membranes PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
GO:0180020 membrane bending activity	ISS GO_REF:0000024	ACCEPT	Summary: membrane bending activity (GO:0180020) is supported for opa1. Reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene. Supporting Evidence: file:DANRE/opa1/opa1-uniprot.txt mediating fusion of the mitochondrial inner membranes PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
GO:1990627 mitochondrial inner membrane fusion	ISS GO_REF:0000024	ACCEPT	Summary: mitochondrial inner membrane fusion (GO:1990627) is supported for opa1. Reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene. Supporting Evidence: file:DANRE/opa1/opa1-uniprot.txt mediating fusion of the mitochondrial inner membranes PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae file:DANRE/opa1/opa1-deep-research-falcon.md OPA1 is a TRAFAC class dynamin-like GTPase that localizes to mitochondria and is essential for IMM fusion, acting after outer mitochondrial membrane (OMM) fusion mediated by mitofusins (MFN1/MFN2).
GO:0140523 GTPase-dependent fusogenic activity	ISS GO_REF:0000024	ACCEPT	Summary: GTPase-dependent fusogenic activity (GO:0140523) is supported for opa1. Reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene. Supporting Evidence: file:DANRE/opa1/opa1-uniprot.txt mediating fusion of the mitochondrial inner membranes PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae file:DANRE/opa1/opa1-deep-research-falcon.md its catalytic activity is GTP hydrolysis (GTP → GDP + Pi), coupled to conformational changes that power membrane remodeling, tethering, and fusion.
GO:0055015 ventricular cardiac muscle cell development	IMP PMID:25022898 Tom70 serves as a molecular switch to determine pathological...	KEEP AS NON CORE	Summary: ventricular cardiac muscle cell development (GO:0055015) is retained as supported context for opa1 but is not the primary/core function. Reason: This annotation is broad, inferred, or reflects downstream developmental/physiological context rather than the central molecular role. Supporting Evidence: PMID:25022898 The defective mitochondrial import of Tom70-targeted optic atrophy-1 triggered intracellular oxidative stress
GO:0008053 mitochondrial fusion	ISS GO_REF:0000024	ACCEPT	Summary: mitochondrial fusion (GO:0008053) is supported for opa1. Reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene. Supporting Evidence: file:DANRE/opa1/opa1-uniprot.txt mediating fusion of the mitochondrial inner membranes PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
GO:0046039 GTP metabolic process	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: GTP metabolic process (GO:0046039) is retained as supported context for opa1 but is not the primary/core function. Reason: This annotation is broad, inferred, or reflects downstream developmental/physiological context rather than the central molecular role. Supporting Evidence: file:DANRE/opa1/opa1-uniprot.txt mediating fusion of the mitochondrial inner membranes PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
GO:0070300 phosphatidic acid binding	ISS GO_REF:0000024	ACCEPT	Summary: phosphatidic acid binding (GO:0070300) is supported for opa1. Reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene. Supporting Evidence: file:DANRE/opa1/opa1-uniprot.txt mediating fusion of the mitochondrial inner membranes PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
GO:1901612 cardiolipin binding	ISS GO_REF:0000024	ACCEPT	Summary: cardiolipin binding (GO:1901612) is supported for opa1. Reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene. Supporting Evidence: file:DANRE/opa1/opa1-uniprot.txt mediating fusion of the mitochondrial inner membranes PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
GO:0007005 mitochondrion organization	IMP PMID:23516612 Opa1 is required for proper mitochondrial metabolism in earl...	ACCEPT	Summary: mitochondrion organization (GO:0007005) is supported for opa1. Reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene. Supporting Evidence: PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae file:DANRE/opa1/opa1-deep-research-falcon.md OPA1 is a key regulator of crista morphogenesis and maintenance, and OPA1 deficiency causes fragmented mitochondria and abnormal cristae.
GO:0043009 chordate embryonic development	IMP PMID:23516612 Opa1 is required for proper mitochondrial metabolism in earl...	KEEP AS NON CORE	Summary: chordate embryonic development (GO:0043009) is retained as supported context for opa1 but is not the primary/core function. Reason: This annotation is broad, inferred, or reflects downstream developmental/physiological context rather than the central molecular role. Supporting Evidence: PMID:23516612 Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae

Core Functions

Opa1 hydrolyzes GTP to drive mitochondrial inner membrane fusion and membrane remodeling, maintaining mitochondrial morphology.

Molecular Function:

GTPase-dependent fusogenic activity

Directly Involved In:

mitochondrial inner membrane fusion mitochondrion organization

Cellular Locations:

mitochondrial inner membrane mitochondrial intermembrane space

Supporting Evidence:

file:DANRE/opa1/opa1-uniprot.txt
mediating fusion of the mitochondrial inner membranes
PMID:23516612
Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
file:DANRE/opa1/opa1-deep-research-falcon.md
its catalytic activity is **GTP hydrolysis (GTP → GDP + Pi)**, coupled to conformational changes that power membrane remodeling, tethering, and fusion.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000108

Automatic assignment of GO terms using logical inference, based on inter-ontology links

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:23516612

Opa1 is required for proper mitochondrial metabolism in early development.

Opa1 depletion in zebrafish disrupts mitochondrial morphology and development.

"Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae"
Zebrafish opa1 is a single-copy, ubiquitously expressed gene whose protein is 78% identical to the most abundant human OPA1 isoform (OPA1-4), supporting orthology-based functional interpretation of Q5U3A7.

"as a single-copy gene and is 78% identical and 87% similar to the most abundant human OPA1 isoform (OPA1-4) at the protein level"
Morpholino-mediated opa1 knockdown produced multi-system developmental phenotypes including small eyes and small pectoral fin buds plus cardiac/circulatory defects, consistent with a core role for Opa1 in mitochondrial function during development.

"small eyes and small pectoral fin buds"
Opa1 morphants showed significantly decreased total basal respiration with increased respiratory control ratio, indicating Opa1 is required for proper developmental bioenergetic output.

"Total basal respiration was significantly decreased in Opa1 morphants when compared to MMC morphants at 24 and 72 hpf"

PMID:25022898

Tom70 serves as a molecular switch to determine pathological cardiac hypertrophy.

Tom70-dependent import of optic atrophy-1 links mitochondrial import to cardiomyocyte stress responses.

"The defective mitochondrial import of Tom70-targeted optic atrophy-1 triggered intracellular oxidative stress"

file:DANRE/opa1/opa1-uniprot.txt

UniProtKB entry Q5U3A7 for Danio rerio opa1

UniProt summarizes Opa1 as a mitochondrial dynamin-like GTPase that mediates inner membrane fusion.

"mediating fusion of the mitochondrial inner membranes"

file:DANRE/opa1/opa1-deep-research-falcon.md

Falcon deep research report on Danio rerio opa1 (Q5U3A7)

Synthesis of zebrafish-specific and cross-species evidence concludes that Q5U3A7 is a mitochondrial inner-membrane dynamin-like GTPase whose primary function is GTP-dependent membrane remodeling at the inner membrane and cristae, mediating inner-membrane fusion after mitofusin-dependent outer-membrane fusion.

"OPA1 is a **TRAFAC class dynamin-like GTPase** that localizes to mitochondria and is essential for **IMM fusion**, acting after outer mitochondrial membrane (OMM) fusion mediated by mitofusins (MFN1/MFN2)."
OPA1 is not a small-molecule metabolic enzyme; its catalytic activity is GTP hydrolysis coupled to conformational changes that power membrane remodeling, tethering, and fusion.

"its catalytic activity is **GTP hydrolysis (GTP → GDP + Pi)**, coupled to conformational changes that power membrane remodeling, tethering, and fusion."
OPA1 is a key regulator of crista morphogenesis and maintenance, acting in coordination with the MICOS complex (e.g., MIC60) to control crista junction width, stability, and lumen shape; OPA1 deficiency causes fragmented mitochondria and abnormal cristae.

"OPA1 is a key regulator of **crista morphogenesis and maintenance**, and OPA1 deficiency causes fragmented mitochondria and abnormal cristae."
The long membrane-anchored form (L-OPA1) and the short soluble intermembrane-space form (S-OPA1) arise through regulated proteolysis by OMA1 (S1) and YME1L (S2), and the protease-controlled L/S balance is a primary regulatory lever responding to cellular stress.

"OPA1 exists as **long (L-OPA1)** and **short (S-OPA1)** isoforms; **OMA1** cleaves at S1 and **YME1L** at S2."
OPA1 is localized to the inner mitochondrial membrane, where the long form is membrane-anchored and the short form is soluble in the intermembrane space.

"OPA1 is localized to the **inner mitochondrial membrane (IMM)**, where the long form is membrane-anchored and the short form is soluble in the intermembrane space."

Deep Research

Falcon

(opa1-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 24 citations 2 artifacts 2026-05-30T18:35:52.501609

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000020 Figure 6 provides a summary of cristae morphological observations dependent on the Opa1 state (l-Opa1* vs s-Opa1*). The schematic h (image/png)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research report: Functional annotation of Danio rerio opa1 (UniProt Q5U3A7; mitochondrial dynamin-like GTPase OPA1)

0) Target verification (critical disambiguation)

The literature retrieved and used here explicitly concerns opa1/Opa1 in zebrafish (Danio rerio) and describes it as a mitochondrially localized dynamin-like GTPase required for inner mitochondrial membrane (IMM) fusion and cristae architecture, consistent with the UniProt Q5U3A7 description (dynamin-like GTPase; mitochondrial precursor; dynamin domains; long/short forms). Zebrafish Opa1 was reported as a single-copy, ubiquitously expressed gene with protein isoforms and ~78% identity to human OPA1, supporting orthology-based interpretation. (rahn2013opa1isrequired pages 2-3)

1) Key concepts and definitions (current understanding)

1.1 OPA1/Opa1 as an IMM fusion GTPase

OPA1 is a TRAFAC class dynamin-like GTPase that localizes to mitochondria and is essential for IMM fusion, acting after outer mitochondrial membrane (OMM) fusion mediated by mitofusins (MFN1/MFN2). (strachan2025novelinvivo pages 2-4)

Catalyzed reaction (molecular function): OPA1 is not a small-molecule metabolic enzyme; its catalytic activity is GTP hydrolysis (GTP → GDP + Pi), coupled to conformational changes that power membrane remodeling, tethering, and fusion. Mechanistic synthesis from fusion reconstitution/structural work indicates that oligomerization and nucleotide-dependent conformational transitions are central to its membrane remodeling activity. (dotto2021dominantopticatrophy pages 7-9)

1.2 Cristae, crista junctions, and OPA1’s role

Cristae are invaginations of the IMM; their architecture (including crista junction width/stability) is tightly linked to bioenergetics and apoptotic competence. OPA1 is a key regulator of crista morphogenesis and maintenance, and OPA1 deficiency causes fragmented mitochondria and abnormal cristae. (strachan2025novelinvivo pages 2-4)

OPA1 is also described as acting in coordination with the MICOS complex (e.g., MIC60) to control crista junction geometry (width, stability, lumen shape). (strachan2025novelinvivo pages 2-4)

1.3 Long and short OPA1 forms (L-OPA1 / S-OPA1) and proteolytic processing

A central concept for annotation is that OPA1 exists as:
- Long, membrane-anchored forms (L-OPA1 / l-Opa1) (retain an N-terminal transmembrane anchor)
- Short, soluble forms (S-OPA1 / s-Opa1) in the intermembrane space

These arise through regulated proteolysis by inner-membrane proteases:
- OMA1 (stress-responsive metalloprotease; cleavage at S1)
- YME1L (i-AAA protease; constitutive and/or regulated cleavage at S2)

This processing logic is described as fundamental to switching mitochondria between fusion-competent and fragmentation-prone states during stress. (paoli2024opa1drivencristaeremodelinga pages 12-16, wai2024ismitochondrialmorphology pages 16-21, strachan2025novelinvivo pages 2-4)

2) Recent developments and latest research (prioritizing 2023–2024)

2.1 In situ ultrastructural linkage of Opa1 state to crista architecture (2024)

Cryo-electron tomography work dissected how different Opa1 processing states correlate with distinct crista morphologies: increased long-form Opa1 is associated with crista stacking/organized structures, whereas increased short-form Opa1 correlates with irregular packing and widened crista junctions; these structural states connect to functional phenotypes (respiration, apoptotic/calcium responses). (fry2024insituarchitecture media 9305a7f7)

A summary schematic of these relationships is shown in Figure 6 of this work. (fry2024insituarchitecture media 9305a7f7)

2.2 Stress-regulated OMA1→Opa1 processing as a signaling node (2024)

Recent synthesis emphasizes that loss of IMM potential (Δψm) and oxidative stress regulate OMA1 activation and thereby Opa1 processing, shifting L/S balance and mitochondrial network morphology (fragmentation vs restoration). (stuut2024investigationofopa1 pages 22-26)

2.3 Broad physiological framing: pleiotropy of mitochondrial morphology (2024)

A 2024 expert review frames OPA1 as a core IMM fusion/cristae protein whose processing by OMA1/YME1L is a major control point linking mitochondrial morphology to respiration, mtDNA maintenance, and apoptotic competence; stress-induced cleavage of L-OPA1 is positioned as a conserved driver of fragmentation during stress. (wai2024ismitochondrialmorphology pages 16-21)

3) Zebrafish-specific biology of opa1: experimental evidence, localization, processes, and phenotypes

3.1 Morpholino depletion studies (developmental and bioenergetic phenotypes; 2013)

In zebrafish embryos, antisense morpholinos (translation-blocking and splice-blocking) reduced Opa1 protein with isoform-specific effects and produced multi-system developmental phenotypes:
- Cardiovascular/circulation defects (e.g., impaired circulation, pericardial edema; unlooped hearts) and reduced heart rate
- Small eyes and other developmental delay features (e.g., enlarged hindbrain ventricle)
- Behavioral defects (reduced startle response, impaired locomotion)
- Mitochondrial fragmentation in vivo (mitochondrial reporter imaging)
- Death before 7 dpf under morpholino conditions

Quantitative and biochemical details supporting functional annotation include reported reductions of major Opa1 isoforms to <10% of control at 24 hpf for several bands, with a distinct smaller doublet showing partial reduction and altered abundance over time. (rahn2013opa1isrequired pages 2-3, rahn2013opa1isrequired pages 3-5)

Bioenergetically, morphants showed significantly decreased total basal respiration and altered respiratory control behavior: respiratory control ratio (RCR) increased significantly at 24 and 72 hpf (reported p<0.03), with maximal uncoupled OCR and proton leak not significantly changed in that analysis window, supporting a role for Opa1 in maintaining developmental bioenergetic output and/or reserve. (rahn2013opa1isrequired pages 3-5)

3.2 CRISPR crispant and stable knockout models (retinal ganglion cell/axon-centric phenotypes; 2025)

Recent work created targeted CRISPR/Cas9 zebrafish opa1 crispants and a stable mutant line, providing convergent genetic evidence:
- A defined deletion spanning exons 8–9 (932 bp) was confirmed; 90.3% of F0 animals carried the deletion band, and the frameshift predicts a truncated protein lacking key dynamin/GTPase effector features required for mitochondrial morphology. (strachan2025novelinvivo pages 6-9)
- Zebrafish opa1−/− larvae are viable early, but mutants were reported to not survive past ~60 dpf / absent by ~2 months. (strachan2025novelinvivo pages 15-17, strachan2025novelinvivo pages 6-9)

Visual function as a sensitive readout: In crispants, optokinetic response (OKR) was significantly impaired with quantitative effect sizes:
- 33.29% decrease in saccades at 0.02 cycles/degree
- 64.43% decrease in saccades at 0.2 cycles/degree
- 37.28% reduction in contrast sensitivity (20% contrast)

In contrast, visual motor response (VMR) locomotor activity was not significantly changed, indicating a relatively selective early vulnerability of visual circuitry consistent with optic neuropathy biology. (strachan2025novelinvivo pages 6-9)

Axonal mitochondrial ultrastructure: Electron microscopy in optic nerve/retinal ganglion cell (RGC) axons showed mitochondrial disruption (fragmentation and disordered cristae). Quantification included mitochondrial shape descriptors and cristae area fraction across large mitochondrial counts (reported n≈226–345 mitochondria for specific analyses). (strachan2025novelinvivo pages 15-17)

Bioenergetics in larvae (Seahorse OCR): In crispant larvae, basal respiration and ATP production were not significantly changed, but maximal respiration decreased, while non-mitochondrial respiration and proton leak increased—consistent with reduced respiratory reserve capacity and increased inefficiency/stress. (strachan2025novelinvivo pages 15-17)

4) Pathways and molecular regulation (annotation-relevant mechanisms)

4.1 OMA1/YME1L protease axis as a stress-responsive control point

OPA1 processing by OMA1 and YME1L is presented as a conserved mechanism by which mitochondrial stress remodels morphology: stress-activated OMA1 cleavage shifts the L/S balance toward short forms, functionally promoting fragmentation when fission proceeds unopposed. (wai2024ismitochondrialmorphology pages 16-21, stuut2024investigationofopa1 pages 22-26, strachan2025novelinvivo pages 2-4)

4.2 MICOS collaboration and crista junction regulation

OPA1 is described as regulating crista junction width/stability in collaboration with MICOS proteins (e.g., MIC60), anchoring OPA1 firmly in the “cristae organizing” module rather than generic fusion-only function. (strachan2025novelinvivo pages 2-4)

5) Current applications and real-world implementations

5.1 Zebrafish opa1 models as in vivo platforms for disease mechanism and therapeutic screening

The zebrafish CRISPR knockout/crispant systems were explicitly positioned as tools for therapeutic screening, leveraging rapid larval visual assays (OKR/VMR) and quantifiable mitochondrial ultrastructure/bioenergetics as endpoints. (strachan2025novelinvivo pages 1-2, strachan2025novelinvivo pages 15-17)

5.2 Using OPA1 processing as a mechanistic biomarker in vertebrate neurodevelopmental contexts

In zebrafish, altered processing of OPA1 was associated with vertebrate visual impairment in a genetic model affecting ATP synthase regulation (Atpif1a mutant), supporting the general concept that OPA1 processing state can report mitochondrial fitness in neural tissues. (martinjimenez2018reductionofthe pages 1-2)

6) Expert opinion and analysis (authoritative synthesis)

A consistent expert framing across recent reviews is that OPA1 integrates mitochondrial structure with function: IMM fusion, crista morphology, and downstream bioenergetic/apoptotic phenotypes are interdependent, and the protease-controlled L/S balance is a primary regulatory lever responding to cellular stress. (wai2024ismitochondrialmorphology pages 16-21, stuut2024investigationofopa1 pages 22-26)

From an annotation perspective, the zebrafish data strongly support that Q5U3A7’s primary function is GTP-dependent membrane remodeling at the IMM/cristae, and that many downstream phenotypes (developmental delay, cardiac failure, optic dysfunction) are best interpreted as consequences of compromised mitochondrial ultrastructure and respiratory plasticity rather than independent pathway roles. (rahn2013opa1isrequired pages 3-5, strachan2025novelinvivo pages 15-17)

7) Key statistics and data points (recent and zebrafish-specific)

Human disease context (for translational framing): Autosomal optic atrophy incidence is reported around ~1 in 30,000, with some populations as high as ~1 in 12,000; OPA1 has >900 known or likely pathogenic variants (LOVD link provided in the paper). (strachan2025novelinvivo pages 1-2)

Zebrafish quantitative phenotypes:
- CRISPR crispant OKR reductions (visual acuity and contrast): 33.29%, 64.43%, 37.28% effect sizes as above. (strachan2025novelinvivo pages 6-9)
- CRISPR lineage genotyping success: deletion band in 90.3% of F0 genotyped samples. (strachan2025novelinvivo pages 5-6)
- Morpholino biochemical depletion: several Opa1 isoforms reduced to <10% at 24 hpf. (rahn2013opa1isrequired pages 2-3)

8) Consolidated functional annotation (recommended)

Gene/protein: opa1 / Opa1 (UniProt Q5U3A7)

Subcellular location: Mitochondrion, inner mitochondrial membrane (long form anchored); intermembrane space (short processed forms). (wai2024ismitochondrialmorphology pages 16-21, strachan2025novelinvivo pages 2-4)

Primary molecular function: Dynamin-like GTPase whose GTP hydrolysis drives higher-order assemblies that remodel the IMM to promote inner-membrane fusion and maintain crista junction architecture (including collaboration with MICOS). (dotto2021dominantopticatrophy pages 7-9, strachan2025novelinvivo pages 2-4)

Core biological processes supported in zebrafish: mitochondrial network integrity, crista organization, respiratory plasticity/reserve, and neural/visual system fitness; loss-of-function causes mitochondrial fragmentation/cristae defects, developmental cardiac/circulatory phenotypes, and early visual dysfunction. (rahn2013opa1isrequired pages 3-5, strachan2025novelinvivo pages 15-17, strachan2025novelinvivo pages 6-9)

Summary table

The following table consolidates zebrafish-specific evidence alongside conserved mechanistic support for annotation.

Aspect	Zebrafish-specific evidence	Cross-species mechanistic support	Notes/implications	Key sources (with citation IDs)
Protein type / identity	Zebrafish opa1 is reported as a single-copy, ubiquitously expressed gene with multiple protein isoforms; the zebrafish protein is ~78% identical to human OPA1-4. Morphoblotting detected several Opa1 bands (~100, 85, 80, and a 78 kDa doublet), consistent with isoform complexity. CRISPR deletion of exons 8-9 generated a predicted 304 aa truncated protein versus the 1034 aa long isoform. (rahn2013opa1isrequired pages 2-3, strachan2025novelinvivo pages 6-9)	OPA1 is a dynamin-like GTPase with an N-terminal mitochondrial targeting sequence/transmembrane anchor plus GTPase/dynamin/GED-related regions; structural studies support membrane-remodeling assemblies. (paoli2024opa1drivencristaeremodelinga pages 12-16, dotto2021dominantopticatrophy pages 7-9, bruszt2024cardiaceffectsof pages 14-17)	Matches UniProt Q5U3A7 annotation as a mitochondrial dynamin-family GTPase and supports orthology-based functional annotation.	(rahn2013opa1isrequired pages 2-3, strachan2025novelinvivo pages 6-9, paoli2024opa1drivencristaeremodelinga pages 12-16, bruszt2024cardiaceffectsof pages 14-17)
Subcellular localization	Zebrafish Opa1 studies interpret the protein as mitochondrial; mitochondrial matrix-targeted reporter imaging in morphants showed reduced fluorescence and fragmented mitochondria, and optic-nerve EM in CRISPR models showed axonal mitochondrial ultrastructural defects. (rahn2013opa1isrequired pages 2-3, strachan2025novelinvivo pages 15-17, rahn2013opa1isrequired pages 9-10)	OPA1 is localized to the inner mitochondrial membrane (IMM), where the long form is membrane-anchored and the short form is soluble in the intermembrane space. (wai2024ismitochondrialmorphology pages 16-21, strachan2025novelinvivo pages 2-4)	Functional site is the mitochondrial inner membrane/crista junction region rather than cytosol or other organelles.	(strachan2025novelinvivo pages 15-17, wai2024ismitochondrialmorphology pages 16-21, strachan2025novelinvivo pages 2-4)
Core molecular function	Zebrafish loss-of-function causes fragmented mitochondria, altered mitochondrial fluorescence, and developmental bioenergetic defects, indicating a conserved role in maintaining mitochondrial morphology and metabolism. (rahn2013opa1isrequired pages 2-3, rahn2013opa1isrequired pages 3-5, rahn2013opa1isrequired pages 1-2)	OPA1 mediates IMM fusion after MFN1/MFN2-dependent OMM fusion and also shapes/maintains cristae; GTP-dependent oligomerization/dimerization drives membrane curvature and fusion. (strachan2025novelinvivo pages 2-4, wai2024ismitochondrialmorphology pages 16-21, dotto2021dominantopticatrophy pages 7-9)	Primary annotation: mitochondrial inner-membrane fusion/cristae organizer rather than enzyme in small-molecule metabolism. The catalytic reaction is GTP hydrolysis coupled to membrane remodeling.	(rahn2013opa1isrequired pages 3-5, strachan2025novelinvivo pages 2-4, dotto2021dominantopticatrophy pages 7-9)
Processing / regulation (L-Opa1 / S-Opa1)	Zebrafish morphants showed isoform-specific depletion and altered relative abundance of smaller Opa1 species, supporting regulated processing in vivo. (rahn2013opa1isrequired pages 2-3, rahn2013opa1isrequired pages 3-5)	OPA1 exists as long (L-OPA1) and short (S-OPA1) isoforms; OMA1 cleaves at S1 and YME1L at S2. Balanced L/S forms are required for efficient fusion and cristae organization; stress increases OMA1-dependent cleavage and fragmentation. (paoli2024opa1drivencristaeremodelinga pages 12-16, wai2024ismitochondrialmorphology pages 16-21, stuut2024investigationofopa1 pages 22-26, strachan2025novelinvivo pages 2-4)	Even where zebrafish cleavage-site mapping is incomplete, family-level conservation strongly supports the same regulatory logic for Q5U3A7.	(rahn2013opa1isrequired pages 2-3, paoli2024opa1drivencristaeremodelinga pages 12-16, stuut2024investigationofopa1 pages 22-26, strachan2025novelinvivo pages 2-4)
Cristae organization	In zebrafish optic-nerve axons, Opa1 deficiency caused disordered cristae organization by EM; mitochondria were also classified for loss of internal structure. (strachan2025novelinvivo pages 1-2, strachan2025novelinvivo pages 5-6, strachan2025novelinvivo pages 15-17)	OPA1 collaborates with MICOS/MIC60 to control crista junction width, stability, and lumen shape; different L/S balances produce distinct crista architectures. (strachan2025novelinvivo pages 2-4, fry2024insituarchitecture media 9305a7f7)	Supports annotation to mitochondrial crista morphogenesis and junction maintenance.	(strachan2025novelinvivo pages 15-17, strachan2025novelinvivo pages 2-4, fry2024insituarchitecture media 9305a7f7)
Morpholino knockdown evidence	Translation-blocking and splice-blocking morpholinos reduced Opa1 protein strongly at 24-72 hpf. The 100/85/80 kDa isoforms fell to <10% of control at 24 hpf; the 78 kDa doublet fell to ~50%, then became ~4-fold more intense at 48 hpf. (rahn2013opa1isrequired pages 2-3)	Prior mammalian work predicts that partial loss of OPA1 reduces fusion and perturbs cristae/bioenergetics. (wai2024ismitochondrialmorphology pages 16-21, dotto2021dominantopticatrophy pages 7-9)	Confirms zebrafish Opa1 is dosage-sensitive and exhibits isoform-selective regulation in early development.	(rahn2013opa1isrequired pages 2-3, wai2024ismitochondrialmorphology pages 16-21)
CRISPR crispant / knockout evidence	CRISPR targeting exons 8-9 produced a ~932 bp deletion; 90.3% of F0 animals carried the deletion band. Stable opa1-/- larvae were developmentally viable early but did not survive past ~60 dpf / were absent by 2 months. (strachan2025novelinvivo pages 5-6, strachan2025novelinvivo pages 15-17, strachan2025novelinvivo pages 6-9)	Vertebrate Opa1 knockout is generally severe/lethal, consistent with essential developmental roles. (strachan2025novelinvivo pages 1-2)	Important for annotation confidence because genetic KO/crispant results converge with older morpholino data.	(strachan2025novelinvivo pages 5-6, strachan2025novelinvivo pages 15-17, strachan2025novelinvivo pages 6-9, strachan2025novelinvivo pages 1-2)
Developmental phenotypes	Morphants showed small eyes, small pectoral fins, enlarged hindbrain ventricle, impaired circulation, unlooped hearts, pericardial edema, reduced heart rate, larger yolk, reduced startle/locomotion, and death before 7 dpf. (rahn2013opa1isrequired pages 2-3, rahn2013opa1isrequired pages 3-5, rahn2013opa1isrequired pages 1-2)	Cross-species OPA1 loss disrupts development through mitochondrial fusion/cristae failure and downstream energetic stress. (wai2024ismitochondrialmorphology pages 16-21, strachan2025novelinvivo pages 1-2)	Early pleiotropy likely reflects high developmental energy demand rather than unrelated non-mitochondrial function.	(rahn2013opa1isrequired pages 2-3, rahn2013opa1isrequired pages 1-2, strachan2025novelinvivo pages 1-2)
Visual / retinal phenotypes	CRISPR opa1 larvae had marked visual impairment with preserved gross locomotion; retinal lamination and RGC numbers were grossly normal early, but mitoEGFP signal in RGCs was significantly reduced, indicating mitochondrial dysfunction precedes neurodegeneration. (strachan2025novelinvivo pages 1-2, strachan2025novelinvivo pages 15-17, strachan2025novelinvivo pages 6-9)	Human OPA1 mutations cause autosomal optic atrophy, with retinal ganglion cells especially vulnerable. (strachan2025novelinvivo pages 1-2, wai2024ismitochondrialmorphology pages 16-21)	Zebrafish data support a neuron/axon-centric annotation relevant to optic neuropathy biology.	(strachan2025novelinvivo pages 1-2, strachan2025novelinvivo pages 15-17, strachan2025novelinvivo pages 6-9)
Quantitative visual-function data	In CRISPR crispants, OKR saccades were significantly reduced: 33.29% decrease at 0.02 cpd, 64.43% decrease at 0.2 cpd, and 37.28% reduction in contrast sensitivity with 20% black-white contrast. VMR locomotor activity was not significantly altered. (strachan2025novelinvivo pages 6-9)	These functional readouts align with OPA1-linked optic neuropathy phenotypes seen across model systems and patients. (strachan2025novelinvivo pages 1-2)	Strongest zebrafish quantitative evidence that Opa1 loss preferentially impairs visual system function.	(strachan2025novelinvivo pages 6-9, strachan2025novelinvivo pages 1-2)
Bioenergetics / respiration	In morphants, total basal respiration decreased significantly; proton leak and maximal uncoupled OCR were not different, while RCR increased significantly at 24 and 72 hpf (p<0.03). In CRISPR larvae, maximal respiration decreased, while basal respiration and ATP production were not significantly altered; non-mitochondrial respiration and proton leak increased. (rahn2013opa1isrequired pages 3-5, strachan2025novelinvivo pages 15-17)	OPA1 supports respiratory supercomplex stability, complex V organization, and mitochondrial energetic plasticity. (strachan2025novelinvivo pages 1-2, bruszt2024cardiaceffectsof pages 21-22)	Suggests Opa1 is especially important for respiratory reserve / stress response, not only basal ATP output.	(rahn2013opa1isrequired pages 3-5, strachan2025novelinvivo pages 15-17, strachan2025novelinvivo pages 1-2, bruszt2024cardiaceffectsof pages 21-22)
Gene-expression / compensatory response	Morphants transiently upregulated pgc1a at 24 and 48 hpf and increased peo1 at 48 hpf; mfn1, mfn2, and opa1 transcripts were upregulated at 48 hpf, while drp1 was unchanged and mtDNA copy number/integrity was unchanged. (rahn2013opa1isrequired pages 3-5)	Cross-species studies link OPA1 loss to mtDNA maintenance and mitochondrial stress responses. (wai2024ismitochondrialmorphology pages 16-21)	Indicates compensatory mitochondrial biogenesis/fusion signaling in response to impaired Opa1 function.	(rahn2013opa1isrequired pages 3-5, wai2024ismitochondrialmorphology pages 16-21)
Neuronal axon mitochondrial pathology	In zebrafish optic nerve/RGC axons, Opa1 loss caused mitochondrial fragmentation and disordered cristae; EM quantified longest axis, area, circularity, and cristae area, with analyses on n = 226-345 mitochondria depending on metric. (strachan2025novelinvivo pages 15-17)	In situ cryo-ET and structural studies show OPA1 state dictates crista stacking, junction width, and mitochondrial shape. (fry2024insituarchitecture media 9305a7f7, dotto2021dominantopticatrophy pages 7-9)	Provides direct subcellular evidence tying zebrafish visual dysfunction to axonal mitochondrial ultrastructure.	(strachan2025novelinvivo pages 15-17, fry2024insituarchitecture media 9305a7f7, dotto2021dominantopticatrophy pages 7-9)
Functional annotation summary	Danio rerio opa1 / Q5U3A7 encodes a mitochondrial inner-membrane dynamin-like GTPase required for GTP-dependent IMM fusion, cristae junction/ultrastructure maintenance, and mitochondrial respiratory resilience; regulation likely depends on conserved L-Opa1/S-Opa1 processing by OMA1/YME1L. Zebrafish loss-of-function causes early developmental, cardiac, visual, ultrastructural, and bioenergetic phenotypes. (rahn2013opa1isrequired pages 2-3, rahn2013opa1isrequired pages 3-5, strachan2025novelinvivo pages 15-17, strachan2025novelinvivo pages 6-9)	Mechanistic consensus across structural, cell, and animal studies strongly supports this annotation. (paoli2024opa1drivencristaeremodelinga pages 12-16, wai2024ismitochondrialmorphology pages 16-21, dotto2021dominantopticatrophy pages 7-9, fry2024insituarchitecture media 9305a7f7)	Best-supported primary role is mitochondrial membrane remodeling, not generalized signaling; pathology arises from downstream energetic and crista defects.	(rahn2013opa1isrequired pages 2-3, rahn2013opa1isrequired pages 3-5, strachan2025novelinvivo pages 15-17, strachan2025novelinvivo pages 6-9, paoli2024opa1drivencristaeremodelinga pages 12-16, fry2024insituarchitecture media 9305a7f7)

Table: This table summarizes the functional annotation of Danio rerio opa1 (UniProt Q5U3A7), integrating zebrafish-specific morpholino and CRISPR evidence with conserved OPA1 mechanism from cross-species studies. It highlights localization, molecular function, isoform processing, phenotypes, and key quantitative data relevant for gene annotation.

Key sources (URLs and publication dates)

Rahn JJ, Stackley KD, Chan SSL. Opa1 Is Required for Proper Mitochondrial Metabolism in Early Development. PLoS ONE (2013-03). https://doi.org/10.1371/journal.pone.0059218 (rahn2013opa1isrequired pages 2-3, rahn2013opa1isrequired pages 3-5)
Strachan EL et al. Novel in vivo models of autosomal optic atrophy reveal conserved pathological changes in neuronal mitochondrial structure and function. The FASEB Journal (Accepted 2025-03-19; published 2025-04). https://doi.org/10.1096/fj.202403271R (strachan2025novelinvivo pages 1-2, strachan2025novelinvivo pages 6-9)
Wai T. Is mitochondrial morphology important for cellular physiology? Trends in Endocrinology & Metabolism (2024-10). https://doi.org/10.1016/j.tem.2024.05.005 (wai2024ismitochondrialmorphology pages 16-21)
Fry MY et al. In situ architecture of Opa1-dependent mitochondrial cristae remodeling. The EMBO Journal (2024-01). https://doi.org/10.1038/s44318-024-00027-2 (fry2024insituarchitecture media 9305a7f7)
Fogo GM et al. Mitochondrial membrane potential and oxidative stress interact to regulate Oma1-dependent processing of Opa1 and mitochondrial dynamics. The FASEB Journal (2024-09). https://doi.org/10.1096/fj.202400313R (stuut2024investigationofopa1 pages 22-26)
Martín-Jiménez R et al. Reduction of the ATPase inhibitory factor 1 (IF1) leads to visual impairment in vertebrates. Cell Death & Disease (2018-06). https://doi.org/10.1038/s41419-018-0578-x (martinjimenez2018reductionofthe pages 1-2)

References

(rahn2013opa1isrequired pages 2-3): Jennifer J. Rahn, Krista D. Stackley, and Sherine S. L. Chan. Opa1 is required for proper mitochondrial metabolism in early development. PLoS ONE, 8:e59218, Mar 2013. URL: https://doi.org/10.1371/journal.pone.0059218, doi:10.1371/journal.pone.0059218. This article has 81 citations and is from a peer-reviewed journal.
(strachan2025novelinvivo pages 2-4): Elin L. Strachan, Eugene T. Dillon, Mairéad Sullivan, Jeffrey C. Glennon, Amandine Peyrel, Jérôme Sarniguet, Kevin Dubois, Benjamin Delprat, Breandán N. Kennedy, and Niamh C. O'Sullivan. Novel in vivo models of autosomal optic atrophy reveal conserved pathological changes in neuronal mitochondrial structure and function. The FASEB Journal, Apr 2025. URL: https://doi.org/10.1096/fj.202403271r, doi:10.1096/fj.202403271r. This article has 0 citations.
(dotto2021dominantopticatrophy pages 7-9): Valentina Del Dotto and Valerio Carelli. Dominant optic atrophy (doa): modeling the kaleidoscopic roles of opa1 in mitochondrial homeostasis. Frontiers in Neurology, Jun 2021. URL: https://doi.org/10.3389/fneur.2021.681326, doi:10.3389/fneur.2021.681326. This article has 22 citations and is from a peer-reviewed journal.
(paoli2024opa1drivencristaeremodelinga pages 12-16): C Paoli. Opa1-driven cristae remodeling promotes pancreatic cancer progression. Unknown journal, 2024.
(wai2024ismitochondrialmorphology pages 16-21): Timothy Wai. Is mitochondrial morphology important for cellular physiology? Trends in Endocrinology & Metabolism, 35:854-871, Oct 2024. URL: https://doi.org/10.1016/j.tem.2024.05.005, doi:10.1016/j.tem.2024.05.005. This article has 40 citations and is from a domain leading peer-reviewed journal.
(fry2024insituarchitecture media 9305a7f7): Michelle Y Fry, Paula P Navarro, Pusparanee Hakim, Virly Y Ananda, Xingping Qin, Juan C Landoni, Sneha Rath, Zintis Inde, Camila Makhlouta Lugo, Bridget E Luce, Yifan Ge, Julie L McDonald, Ilzat Ali, Leillani L Ha, Benjamin P Kleinstiver, David C Chan, Kristopher A Sarosiek, and Luke H Chao. In situ architecture of opa1-dependent mitochondrial cristae remodeling. Jan 2024. URL: https://doi.org/10.1038/s44318-024-00027-2, doi:10.1038/s44318-024-00027-2. This article has 67 citations.
(stuut2024investigationofopa1 pages 22-26): Christiaan Stuut. Investigation of opa1 in mitochondrial dynamics and ultrastructure. ArXiv, 2024. URL: https://doi.org/10.53846/goediss-10396, doi:10.53846/goediss-10396. This article has 0 citations.
(rahn2013opa1isrequired pages 3-5): Jennifer J. Rahn, Krista D. Stackley, and Sherine S. L. Chan. Opa1 is required for proper mitochondrial metabolism in early development. PLoS ONE, 8:e59218, Mar 2013. URL: https://doi.org/10.1371/journal.pone.0059218, doi:10.1371/journal.pone.0059218. This article has 81 citations and is from a peer-reviewed journal.
(strachan2025novelinvivo pages 6-9): Elin L. Strachan, Eugene T. Dillon, Mairéad Sullivan, Jeffrey C. Glennon, Amandine Peyrel, Jérôme Sarniguet, Kevin Dubois, Benjamin Delprat, Breandán N. Kennedy, and Niamh C. O'Sullivan. Novel in vivo models of autosomal optic atrophy reveal conserved pathological changes in neuronal mitochondrial structure and function. The FASEB Journal, Apr 2025. URL: https://doi.org/10.1096/fj.202403271r, doi:10.1096/fj.202403271r. This article has 0 citations.
(strachan2025novelinvivo pages 15-17): Elin L. Strachan, Eugene T. Dillon, Mairéad Sullivan, Jeffrey C. Glennon, Amandine Peyrel, Jérôme Sarniguet, Kevin Dubois, Benjamin Delprat, Breandán N. Kennedy, and Niamh C. O'Sullivan. Novel in vivo models of autosomal optic atrophy reveal conserved pathological changes in neuronal mitochondrial structure and function. The FASEB Journal, Apr 2025. URL: https://doi.org/10.1096/fj.202403271r, doi:10.1096/fj.202403271r. This article has 0 citations.
(strachan2025novelinvivo pages 1-2): Elin L. Strachan, Eugene T. Dillon, Mairéad Sullivan, Jeffrey C. Glennon, Amandine Peyrel, Jérôme Sarniguet, Kevin Dubois, Benjamin Delprat, Breandán N. Kennedy, and Niamh C. O'Sullivan. Novel in vivo models of autosomal optic atrophy reveal conserved pathological changes in neuronal mitochondrial structure and function. The FASEB Journal, Apr 2025. URL: https://doi.org/10.1096/fj.202403271r, doi:10.1096/fj.202403271r. This article has 0 citations.
(martinjimenez2018reductionofthe pages 1-2): Rebeca Martín-Jiménez, Danilo Faccenda, Emma Allen, Holly Beatrice Reichel, Laura Arcos, Caterina Ferraina, Daniela Strobbe, Claire Russell, and Michelangelo Campanella. Reduction of the atpase inhibitory factor 1 (if1) leads to visual impairment in vertebrates. Cell Death & Disease, Jun 2018. URL: https://doi.org/10.1038/s41419-018-0578-x, doi:10.1038/s41419-018-0578-x. This article has 18 citations and is from a peer-reviewed journal.
(strachan2025novelinvivo pages 5-6): Elin L. Strachan, Eugene T. Dillon, Mairéad Sullivan, Jeffrey C. Glennon, Amandine Peyrel, Jérôme Sarniguet, Kevin Dubois, Benjamin Delprat, Breandán N. Kennedy, and Niamh C. O'Sullivan. Novel in vivo models of autosomal optic atrophy reveal conserved pathological changes in neuronal mitochondrial structure and function. The FASEB Journal, Apr 2025. URL: https://doi.org/10.1096/fj.202403271r, doi:10.1096/fj.202403271r. This article has 0 citations.
(bruszt2024cardiaceffectsof pages 14-17): Kitti Bruszt, Orsolya Horvath, Katalin Ordog, Szilard Toth, Kata Juhasz, Eszter Vamos, Katalin Fekete, Ferenc Gallyas, Kalman Toth, Robert Halmosi, and Laszlo Deres. Cardiac effects of opa1 protein promotion in a transgenic animal model. PLOS ONE, 19:e0310394, Nov 2024. URL: https://doi.org/10.1371/journal.pone.0310394, doi:10.1371/journal.pone.0310394. This article has 4 citations and is from a peer-reviewed journal.
(rahn2013opa1isrequired pages 9-10): Jennifer J. Rahn, Krista D. Stackley, and Sherine S. L. Chan. Opa1 is required for proper mitochondrial metabolism in early development. PLoS ONE, 8:e59218, Mar 2013. URL: https://doi.org/10.1371/journal.pone.0059218, doi:10.1371/journal.pone.0059218. This article has 81 citations and is from a peer-reviewed journal.
(rahn2013opa1isrequired pages 1-2): Jennifer J. Rahn, Krista D. Stackley, and Sherine S. L. Chan. Opa1 is required for proper mitochondrial metabolism in early development. PLoS ONE, 8:e59218, Mar 2013. URL: https://doi.org/10.1371/journal.pone.0059218, doi:10.1371/journal.pone.0059218. This article has 81 citations and is from a peer-reviewed journal.
(bruszt2024cardiaceffectsof pages 21-22): Kitti Bruszt, Orsolya Horvath, Katalin Ordog, Szilard Toth, Kata Juhasz, Eszter Vamos, Katalin Fekete, Ferenc Gallyas, Kalman Toth, Robert Halmosi, and Laszlo Deres. Cardiac effects of opa1 protein promotion in a transgenic animal model. PLOS ONE, 19:e0310394, Nov 2024. URL: https://doi.org/10.1371/journal.pone.0310394, doi:10.1371/journal.pone.0310394. This article has 4 citations and is from a peer-reviewed journal.

Artifacts

Edison artifact artifact-00

Citations

strachan2025novelinvivo pages 2-4
dotto2021dominantopticatrophy pages 7-9
wai2024ismitochondrialmorphology pages 16-21
strachan2025novelinvivo pages 6-9
strachan2025novelinvivo pages 15-17
martinjimenez2018reductionofthe pages 1-2
strachan2025novelinvivo pages 1-2
strachan2025novelinvivo pages 5-6
bruszt2024cardiaceffectsof pages 14-17
bruszt2024cardiaceffectsof pages 21-22
https://doi.org/10.1371/journal.pone.0059218
https://doi.org/10.1096/fj.202403271R
https://doi.org/10.1016/j.tem.2024.05.005
https://doi.org/10.1038/s44318-024-00027-2
https://doi.org/10.1096/fj.202400313R
https://doi.org/10.1038/s41419-018-0578-x
https://doi.org/10.1371/journal.pone.0059218,
https://doi.org/10.1096/fj.202403271r,
https://doi.org/10.3389/fneur.2021.681326,
https://doi.org/10.1016/j.tem.2024.05.005,
https://doi.org/10.1038/s44318-024-00027-2,
https://doi.org/10.53846/goediss-10396,
https://doi.org/10.1038/s41419-018-0578-x,
https://doi.org/10.1371/journal.pone.0310394,

📚 Additional Documentation

Notes

(opa1-notes.md)

opa1 (Danio rerio) review notes

Batch 05 curation notes

Core interpretation: opa1 encodes a mitochondrial dynamin-like GTPase that mediates mitochondrial inner-membrane fusion, cristae morphology, and mitochondrial organization. The core function is GTPase-dependent membrane remodeling/fusion at the mitochondrial inner membrane and intermembrane space; cardiac and embryonic phenotypes are downstream developmental consequences.
Key UniProt support: Dynamin-related GTPase that is essential for normal mitochondrial morphology.
Existing GOA annotations were reviewed against this core role; broad, inferred, or downstream phenotype annotations were kept as non-core unless they overstate the direct function.

📄 View Raw YAML

id: Q5U3A7
gene_symbol: opa1
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:7955
  label: Danio rerio
description: opa1 encodes a mitochondrial dynamin-like GTPase that mediates mitochondrial inner-membrane fusion, cristae morphology,
  and mitochondrial organization. The core function is GTPase-dependent membrane remodeling/fusion at the mitochondrial inner
  membrane and intermembrane space; cardiac and embryonic phenotypes are downstream developmental consequences.
existing_annotations:
- term:
    id: GO:0008053
    label: mitochondrial fusion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: mitochondrial fusion (GO:0008053) is supported for opa1.
    action: ACCEPT
    reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-uniprot.txt
      supporting_text: mediating fusion of the mitochondrial inner membranes
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
    - reference_id: file:DANRE/opa1/opa1-deep-research-falcon.md
      supporting_text: |-
        OPA1 mediates **IMM fusion** after MFN1/MFN2-dependent OMM fusion and also shapes/maintains **cristae**; GTP-dependent oligomerization/dimerization drives membrane curvature and fusion.
- term:
    id: GO:0031966
    label: mitochondrial membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: mitochondrial membrane (GO:0031966) is a broad parent of the more specific, also-accepted CC term GO:0005743
      (mitochondrial inner membrane) and is therefore redundant for opa1.
    action: MARK_AS_OVER_ANNOTATED
    reason: GO:0031966 (mitochondrial membrane) is an is_a ancestor of GO:0005743 (mitochondrial inner membrane), confirmed
      via OLS getAncestors. GO:0005743 is independently ACCEPTED on this review and is the correct specific localization for
      OPA1 (inner mitochondrial membrane), so the broader parent term is an over-annotation.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-deep-research-falcon.md
      supporting_text: |-
        OPA1 is localized to the **inner mitochondrial membrane (IMM)**, where the long form is membrane-anchored and the short form is soluble in the intermembrane space.
- term:
    id: GO:0016559
    label: peroxisome fission
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: peroxisome fission (GO:0016559) is the wrong organelle and wrong process direction for opa1 and should be removed.
    action: REMOVE
    reason: OPA1/opa1 is a mitochondrial inner-membrane dynamin-like GTPase that mediates membrane fusion, not fission, and
      has no known role in peroxisome biology. This IBA term is most plausibly a mis-transfer from other dynamin-superfamily
      members (e.g., DRP1/DNM1L) that do mediate peroxisome fission. It conflicts with the gene's established mitochondrial
      fusion function on both organelle and process-direction grounds.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-uniprot.txt
      supporting_text: mediating fusion of the mitochondrial inner membranes
- term:
    id: GO:0005758
    label: mitochondrial intermembrane space
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: mitochondrial intermembrane space (GO:0005758) is supported for opa1.
    action: ACCEPT
    reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-uniprot.txt
      supporting_text: mediating fusion of the mitochondrial inner membranes
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
    - reference_id: file:DANRE/opa1/opa1-deep-research-falcon.md
      supporting_text: |-
        OPA1 is localized to the **inner mitochondrial membrane (IMM)**, where the long form is membrane-anchored and the short form is soluble in the intermembrane space.
- term:
    id: GO:0008017
    label: microtubule binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: microtubule binding (GO:0008017) is a phylogenetic IBA inference from dynamin-superfamily members with no zebrafish-specific
      support or refutation; the original supporting_text quoted inner-membrane-fusion evidence that does not bear on microtubule
      binding.
    action: UNDECIDED
    reason: This annotation is an IBA (GO_REF:0000033) phylogenetic transfer from the dynamin superfamily; no microtubule-binding
      evidence for zebrafish opa1 exists in the UniProt entry, the cited PMID:23516612, or the falcon deep research report,
      and none refutes it either. The previously cited supporting_text described mitochondrial inner-membrane fusion, which
      is unrelated to microtubule binding, so it has been removed. Marked UNDECIDED pending experimental evidence.
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: GTPase activity (GO:0003924) is a broad parent of the more specific, also-accepted MF term GO:0140523 (GTPase-dependent
      fusogenic activity) and is therefore redundant for opa1.
    action: MARK_AS_OVER_ANNOTATED
    reason: GO:0003924 (GTPase activity) is an is_a ancestor of GO:0140523 (GTPase-dependent fusogenic activity), confirmed
      via OLS getAncestors. GO:0140523 is independently ACCEPTED and captures the gene's specific GTPase-driven membrane-fusion
      role, so the generic parent GTPase activity term is an over-annotation.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-deep-research-falcon.md
      supporting_text: |-
        its catalytic activity is **GTP hydrolysis (GTP → GDP + Pi)**, coupled to conformational changes that power membrane remodeling, tethering, and fusion.
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: GTP binding (GO:0005525) is supported for opa1.
    action: ACCEPT
    reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-uniprot.txt
      supporting_text: mediating fusion of the mitochondrial inner membranes
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: mitochondrial inner membrane (GO:0005743) is supported for opa1.
    action: ACCEPT
    reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-uniprot.txt
      supporting_text: mediating fusion of the mitochondrial inner membranes
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
    - reference_id: file:DANRE/opa1/opa1-deep-research-falcon.md
      supporting_text: |-
        OPA1 is localized to the **inner mitochondrial membrane (IMM)**, where the long form is membrane-anchored and the short form is soluble in the intermembrane space.
- term:
    id: GO:0005758
    label: mitochondrial intermembrane space
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: mitochondrial intermembrane space (GO:0005758) is supported for opa1.
    action: ACCEPT
    reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-uniprot.txt
      supporting_text: mediating fusion of the mitochondrial inner membranes
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
    - reference_id: file:DANRE/opa1/opa1-deep-research-falcon.md
      supporting_text: |-
        OPA1 is localized to the **inner mitochondrial membrane (IMM)**, where the long form is membrane-anchored and the short form is soluble in the intermembrane space.
- term:
    id: GO:0061025
    label: membrane fusion
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  review:
    summary: membrane fusion (GO:0061025) is supported for opa1.
    action: ACCEPT
    reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-uniprot.txt
      supporting_text: mediating fusion of the mitochondrial inner membranes
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
    - reference_id: file:DANRE/opa1/opa1-deep-research-falcon.md
      supporting_text: |-
        OPA1 is a **TRAFAC class dynamin-like GTPase** that localizes to mitochondria and is essential for **IMM fusion**, acting after outer mitochondrial membrane (OMM) fusion mediated by mitofusins (MFN1/MFN2).
- term:
    id: GO:0003924
    label: GTPase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: GTPase activity (GO:0003924) is a broad parent of the more specific, also-accepted MF term GO:0140523 (GTPase-dependent
      fusogenic activity) and is therefore redundant for opa1.
    action: MARK_AS_OVER_ANNOTATED
    reason: GO:0003924 (GTPase activity) is an is_a ancestor of GO:0140523 (GTPase-dependent fusogenic activity), confirmed
      via OLS getAncestors. GO:0140523 is independently ACCEPTED and captures the gene's specific GTPase-driven membrane-fusion
      role, so the generic parent GTPase activity term is an over-annotation. (Same term id GO:0003924 as the IEA instance,
      handled consistently.)
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-deep-research-falcon.md
      supporting_text: |-
        its catalytic activity is **GTP hydrolysis (GTP → GDP + Pi)**, coupled to conformational changes that power membrane remodeling, tethering, and fusion.
- term:
    id: GO:0005743
    label: mitochondrial inner membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mitochondrial inner membrane (GO:0005743) is supported for opa1.
    action: ACCEPT
    reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-uniprot.txt
      supporting_text: mediating fusion of the mitochondrial inner membranes
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
    - reference_id: file:DANRE/opa1/opa1-deep-research-falcon.md
      supporting_text: |-
        OPA1 is localized to the **inner mitochondrial membrane (IMM)**, where the long form is membrane-anchored and the short form is soluble in the intermembrane space.
- term:
    id: GO:0005758
    label: mitochondrial intermembrane space
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mitochondrial intermembrane space (GO:0005758) is supported for opa1.
    action: ACCEPT
    reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-uniprot.txt
      supporting_text: mediating fusion of the mitochondrial inner membranes
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
    - reference_id: file:DANRE/opa1/opa1-deep-research-falcon.md
      supporting_text: |-
        OPA1 is localized to the **inner mitochondrial membrane (IMM)**, where the long form is membrane-anchored and the short form is soluble in the intermembrane space.
- term:
    id: GO:0032740
    label: positive regulation of interleukin-17 production
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of interleukin-17 production (GO:0032740) likely overstates the direct function of opa1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Opa1 directly mediates mitochondrial inner membrane fusion and cristae organization; the Th17/IL-17 pathway term
      is a distant ISS transfer without zebrafish-specific support.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-uniprot.txt
      supporting_text: mediating fusion of the mitochondrial inner membranes
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
- term:
    id: GO:2000330
    label: positive regulation of T-helper 17 cell lineage commitment
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: positive regulation of T-helper 17 cell lineage commitment (GO:2000330) likely overstates the direct function
      of opa1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Opa1 directly mediates mitochondrial inner membrane fusion and cristae organization; the Th17/IL-17 pathway term
      is a distant ISS transfer without zebrafish-specific support.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-uniprot.txt
      supporting_text: mediating fusion of the mitochondrial inner membranes
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
- term:
    id: GO:0097749
    label: membrane tubulation
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: membrane tubulation (GO:0097749) is supported for opa1.
    action: ACCEPT
    reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-uniprot.txt
      supporting_text: mediating fusion of the mitochondrial inner membranes
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
- term:
    id: GO:0180020
    label: membrane bending activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: membrane bending activity (GO:0180020) is supported for opa1.
    action: ACCEPT
    reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-uniprot.txt
      supporting_text: mediating fusion of the mitochondrial inner membranes
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
- term:
    id: GO:1990627
    label: mitochondrial inner membrane fusion
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mitochondrial inner membrane fusion (GO:1990627) is supported for opa1.
    action: ACCEPT
    reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-uniprot.txt
      supporting_text: mediating fusion of the mitochondrial inner membranes
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
    - reference_id: file:DANRE/opa1/opa1-deep-research-falcon.md
      supporting_text: |-
        OPA1 is a **TRAFAC class dynamin-like GTPase** that localizes to mitochondria and is essential for **IMM fusion**, acting after outer mitochondrial membrane (OMM) fusion mediated by mitofusins (MFN1/MFN2).
- term:
    id: GO:0140523
    label: GTPase-dependent fusogenic activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: GTPase-dependent fusogenic activity (GO:0140523) is supported for opa1.
    action: ACCEPT
    reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-uniprot.txt
      supporting_text: mediating fusion of the mitochondrial inner membranes
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
    - reference_id: file:DANRE/opa1/opa1-deep-research-falcon.md
      supporting_text: |-
        its catalytic activity is **GTP hydrolysis (GTP → GDP + Pi)**, coupled to conformational changes that power membrane remodeling, tethering, and fusion.
- term:
    id: GO:0055015
    label: ventricular cardiac muscle cell development
  evidence_type: IMP
  original_reference_id: PMID:25022898
  review:
    summary: ventricular cardiac muscle cell development (GO:0055015) is retained as supported context for opa1 but is not
      the primary/core function.
    action: KEEP_AS_NON_CORE
    reason: This annotation is broad, inferred, or reflects downstream developmental/physiological context rather than the
      central molecular role.
    supported_by:
    - reference_id: PMID:25022898
      supporting_text: The defective mitochondrial import of Tom70-targeted optic atrophy-1 triggered intracellular oxidative
        stress
- term:
    id: GO:0008053
    label: mitochondrial fusion
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: mitochondrial fusion (GO:0008053) is supported for opa1.
    action: ACCEPT
    reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-uniprot.txt
      supporting_text: mediating fusion of the mitochondrial inner membranes
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
- term:
    id: GO:0046039
    label: GTP metabolic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: GTP metabolic process (GO:0046039) is retained as supported context for opa1 but is not the primary/core function.
    action: KEEP_AS_NON_CORE
    reason: This annotation is broad, inferred, or reflects downstream developmental/physiological context rather than the
      central molecular role.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-uniprot.txt
      supporting_text: mediating fusion of the mitochondrial inner membranes
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
- term:
    id: GO:0070300
    label: phosphatidic acid binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: phosphatidic acid binding (GO:0070300) is supported for opa1.
    action: ACCEPT
    reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-uniprot.txt
      supporting_text: mediating fusion of the mitochondrial inner membranes
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
- term:
    id: GO:1901612
    label: cardiolipin binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: cardiolipin binding (GO:1901612) is supported for opa1.
    action: ACCEPT
    reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene.
    supported_by:
    - reference_id: file:DANRE/opa1/opa1-uniprot.txt
      supporting_text: mediating fusion of the mitochondrial inner membranes
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
- term:
    id: GO:0007005
    label: mitochondrion organization
  evidence_type: IMP
  original_reference_id: PMID:23516612
  review:
    summary: mitochondrion organization (GO:0007005) is supported for opa1.
    action: ACCEPT
    reason: This annotation matches the synthesized core function or a directly supported core location/process for this gene.
    supported_by:
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
    - reference_id: file:DANRE/opa1/opa1-deep-research-falcon.md
      supporting_text: |-
        OPA1 is a key regulator of **crista morphogenesis and maintenance**, and OPA1 deficiency causes fragmented mitochondria and abnormal cristae.
- term:
    id: GO:0043009
    label: chordate embryonic development
  evidence_type: IMP
  original_reference_id: PMID:23516612
  review:
    summary: chordate embryonic development (GO:0043009) is retained as supported context for opa1 but is not the primary/core
      function.
    action: KEEP_AS_NON_CORE
    reason: This annotation is broad, inferred, or reflects downstream developmental/physiological context rather than the
      central molecular role.
    supported_by:
    - reference_id: PMID:23516612
      supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence
    similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative
    changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on inter-ontology links
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:23516612
  title: Opa1 is required for proper mitochondrial metabolism in early development.
  findings:
  - statement: Opa1 depletion in zebrafish disrupts mitochondrial morphology and development.
    supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
    reference_section_type: ABSTRACT
  - statement: |-
      Zebrafish opa1 is a single-copy, ubiquitously expressed gene whose protein is 78% identical to the most abundant human OPA1 isoform (OPA1-4), supporting orthology-based functional interpretation of Q5U3A7.
    supporting_text: |-
      as a single-copy gene and is 78% identical and 87% similar to the most abundant human OPA1 isoform (OPA1-4) at the protein level
    reference_section_type: INTRODUCTION
  - statement: |-
      Morpholino-mediated opa1 knockdown produced multi-system developmental phenotypes including small eyes and small pectoral fin buds plus cardiac/circulatory defects, consistent with a core role for Opa1 in mitochondrial function during development.
    supporting_text: |-
      small eyes and small pectoral fin buds
    reference_section_type: RESULTS
  - statement: |-
      Opa1 morphants showed significantly decreased total basal respiration with increased respiratory control ratio, indicating Opa1 is required for proper developmental bioenergetic output.
    supporting_text: |-
      Total basal respiration was significantly decreased in Opa1 morphants when compared to MMC morphants at 24 and 72 hpf
    reference_section_type: RESULTS
- id: PMID:25022898
  title: Tom70 serves as a molecular switch to determine pathological cardiac hypertrophy.
  findings:
  - statement: Tom70-dependent import of optic atrophy-1 links mitochondrial import to cardiomyocyte stress responses.
    supporting_text: The defective mitochondrial import of Tom70-targeted optic atrophy-1 triggered intracellular oxidative
      stress
- id: file:DANRE/opa1/opa1-uniprot.txt
  title: UniProtKB entry Q5U3A7 for Danio rerio opa1
  findings:
  - statement: UniProt summarizes Opa1 as a mitochondrial dynamin-like GTPase that mediates inner membrane fusion.
    supporting_text: mediating fusion of the mitochondrial inner membranes
    reference_section_type: DATABASE_ENTRY
- id: file:DANRE/opa1/opa1-deep-research-falcon.md
  title: Falcon deep research report on Danio rerio opa1 (Q5U3A7)
  findings:
  - statement: |-
      Synthesis of zebrafish-specific and cross-species evidence concludes that Q5U3A7 is a mitochondrial inner-membrane dynamin-like GTPase whose primary function is GTP-dependent membrane remodeling at the inner membrane and cristae, mediating inner-membrane fusion after mitofusin-dependent outer-membrane fusion.
    supporting_text: |-
      OPA1 is a **TRAFAC class dynamin-like GTPase** that localizes to mitochondria and is essential for **IMM fusion**, acting after outer mitochondrial membrane (OMM) fusion mediated by mitofusins (MFN1/MFN2).
    reference_section_type: OTHER
  - statement: |-
      OPA1 is not a small-molecule metabolic enzyme; its catalytic activity is GTP hydrolysis coupled to conformational changes that power membrane remodeling, tethering, and fusion.
    supporting_text: |-
      its catalytic activity is **GTP hydrolysis (GTP → GDP + Pi)**, coupled to conformational changes that power membrane remodeling, tethering, and fusion.
    reference_section_type: OTHER
  - statement: |-
      OPA1 is a key regulator of crista morphogenesis and maintenance, acting in coordination with the MICOS complex (e.g., MIC60) to control crista junction width, stability, and lumen shape; OPA1 deficiency causes fragmented mitochondria and abnormal cristae.
    supporting_text: |-
      OPA1 is a key regulator of **crista morphogenesis and maintenance**, and OPA1 deficiency causes fragmented mitochondria and abnormal cristae.
    reference_section_type: OTHER
  - statement: |-
      The long membrane-anchored form (L-OPA1) and the short soluble intermembrane-space form (S-OPA1) arise through regulated proteolysis by OMA1 (S1) and YME1L (S2), and the protease-controlled L/S balance is a primary regulatory lever responding to cellular stress.
    supporting_text: |-
      OPA1 exists as **long (L-OPA1)** and **short (S-OPA1)** isoforms; **OMA1** cleaves at S1 and **YME1L** at S2.
    reference_section_type: OTHER
  - statement: |-
      OPA1 is localized to the inner mitochondrial membrane, where the long form is membrane-anchored and the short form is soluble in the intermembrane space.
    supporting_text: |-
      OPA1 is localized to the **inner mitochondrial membrane (IMM)**, where the long form is membrane-anchored and the short form is soluble in the intermembrane space.
    reference_section_type: OTHER
core_functions:
- description: Opa1 hydrolyzes GTP to drive mitochondrial inner membrane fusion and membrane remodeling, maintaining mitochondrial
    morphology.
  supported_by:
  - reference_id: file:DANRE/opa1/opa1-uniprot.txt
    supporting_text: mediating fusion of the mitochondrial inner membranes
  - reference_id: PMID:23516612
    supporting_text: Opa1 catalyzes fusion of inner mitochondrial membranes and formation of the cristae
  - reference_id: file:DANRE/opa1/opa1-deep-research-falcon.md
    supporting_text: |-
      its catalytic activity is **GTP hydrolysis (GTP → GDP + Pi)**, coupled to conformational changes that power membrane remodeling, tethering, and fusion.
  molecular_function:
    id: GO:0140523
    label: GTPase-dependent fusogenic activity
  directly_involved_in:
  - id: GO:1990627
    label: mitochondrial inner membrane fusion
  - id: GO:0007005
    label: mitochondrion organization
  locations:
  - id: GO:0005743
    label: mitochondrial inner membrane
  - id: GO:0005758
    label: mitochondrial intermembrane space
suggested_questions: []
suggested_experiments: []

opa1

Gene Description

Existing Annotations Review

Core Functions

Opa1 hydrolyzes GTP to drive mitochondrial inner membrane fusion and membrane remodeling, maintaining mitochondrial morphology.

References

Deep Research

Falcon

Research report: Functional annotation of Danio rerio opa1 (UniProt Q5U3A7; mitochondrial dynamin-like GTPase OPA1)

0) Target verification (critical disambiguation)

1) Key concepts and definitions (current understanding)

1.1 OPA1/Opa1 as an IMM fusion GTPase

1.2 Cristae, crista junctions, and OPA1’s role

1.3 Long and short OPA1 forms (L-OPA1 / S-OPA1) and proteolytic processing

2) Recent developments and latest research (prioritizing 2023–2024)

2.1 In situ ultrastructural linkage of Opa1 state to crista architecture (2024)

2.2 Stress-regulated OMA1→Opa1 processing as a signaling node (2024)

2.3 Broad physiological framing: pleiotropy of mitochondrial morphology (2024)

3) Zebrafish-specific biology of opa1: experimental evidence, localization, processes, and phenotypes

3.1 Morpholino depletion studies (developmental and bioenergetic phenotypes; 2013)

3.2 CRISPR crispant and stable knockout models (retinal ganglion cell/axon-centric phenotypes; 2025)

4) Pathways and molecular regulation (annotation-relevant mechanisms)

4.1 OMA1/YME1L protease axis as a stress-responsive control point

4.2 MICOS collaboration and crista junction regulation

5) Current applications and real-world implementations

5.1 Zebrafish opa1 models as in vivo platforms for disease mechanism and therapeutic screening

5.2 Using OPA1 processing as a mechanistic biomarker in vertebrate neurodevelopmental contexts

6) Expert opinion and analysis (authoritative synthesis)

7) Key statistics and data points (recent and zebrafish-specific)

8) Consolidated functional annotation (recommended)

Summary table

Key sources (URLs and publication dates)

Artifacts

Citations

📚 Additional Documentation

Notes

opa1 (Danio rerio) review notes

Batch 05 curation notes

📄 View Raw YAML