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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

• UniProt Accession: Q94263
• Protein Description: RecName: Full=Mitochondrial Rho GTPase 1; Short=Miro; EC=3.6.5.-;
• Gene Information: Name=miro-1 {ECO:0000312|WormBase:K08F11.5}; ORFNames=K08F11.5 {ECO:0000312|WormBase:K08F11.5};
• Organism (full): Caenorhabditis elegans.
• Protein Family: Belongs to the mitochondrial Rho GTPase family.
• Key Domains: EF-hand-dom_pair. (IPR011992); EF_Hand_1_Ca_BS. (IPR018247); EF_hand_assoc_1. (IPR013566); EF_hand_assoc_2. (IPR013567); EF_hand_dom. (IPR002048)

MANDATORY VERIFICATION STEPS:

1. Check if the gene symbol "miro-1" matches the protein description above
2. Verify the organism is correct: Caenorhabditis elegans.
3. Check if protein family/domains align with what you find in literature
4. If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'miro-1' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene miro-1 (gene ID: miro-1, UniProt: Q94263) in worm.

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this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.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.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

• UniProt Accession: Q94263
• Protein Description: RecName: Full=Mitochondrial Rho GTPase 1; Short=Miro; EC=3.6.5.-;
• Gene Information: Name=miro-1 {ECO:0000312|WormBase:K08F11.5}; ORFNames=K08F11.5 {ECO:0000312|WormBase:K08F11.5};
• Organism (full): Caenorhabditis elegans.
• Protein Family: Belongs to the mitochondrial Rho GTPase family.
• Key Domains: EF-hand-dom_pair. (IPR011992); EF_Hand_1_Ca_BS. (IPR018247); EF_hand_assoc_1. (IPR013566); EF_hand_assoc_2. (IPR013567); EF_hand_dom. (IPR002048)

MANDATORY VERIFICATION STEPS:

1. Check if the gene symbol "miro-1" matches the protein description above
2. Verify the organism is correct: Caenorhabditis elegans.
3. Check if protein family/domains align with what you find in literature
4. If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'miro-1' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene miro-1 (gene ID: miro-1, UniProt: Q94263) in worm.

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.

Plan of work
- Verified identity and domain architecture for C. elegans miro-1 (K08F11.5; UniProt Q94263), then gathered worm-specific primary literature, prioritizing 2023–2024 sources, and complemented with mechanistic reviews for cross-species context. Extracted quantitative data and organized key studies in an evidence table embedded below (artifact-00). (shen2016c.elegansmiro1 pages 11-13, aspenstrom2024mirogtpasesat pages 3-4)

Comprehensive research report: C. elegans miro-1 (UniProt Q94263)

1) Identity, key concepts, and definitions
- Gene/protein identity: miro-1 (locus K08F11.5) encodes mitochondrial Rho GTPase 1 (Miro), an outer mitochondrial membrane, tail-anchored small GTPase with two GTPase domains (N- and C-terminal) and tandem EF-hand Ca2+-binding motifs; this architecture is conserved across eukaryotes and matches UniProt Q94263. In C. elegans, miro-1(tm1966) is a commonly used loss-of-function allele. (Shen et al., PLoS ONE, 2016; URL: https://doi.org/10.1371/journal.pone.0153233). Mechanistic reviews detail domain functions, Ca2+ sensing by EF hands, and adaptor binding via the C-terminal region. (Aspenström, Cells, 2024; URL: https://doi.org/10.3390/cells13070647) (shen2016c.elegansmiro1 pages 11-13, aspenstrom2024mirogtpasesat pages 3-4)
- Subcellular localization: MIRO-1 is tail-anchored to the outer mitochondrial membrane; in vivo worm studies show MIRO-1 enrichment on fragmented mitochondria during stress and a functional requirement for maintaining mitochondrial membrane potential. (Ren et al., EMBO Reports, 2023; URL: https://doi.org/10.15252/embr.202256297) (ren2023miro‐1interactswith pages 4-5)
- Primary functional concept: Miro proteins link mitochondria to axonal transport machinery and tune motility in response to Ca2+; they also participate in ER–mitochondria contacts and mitochondrial quality control pathways (e.g., PINK1/Parkin-mediated mitophagy regulation across species). (Aspenström, 2024; Tang, 2015; URLs: https://doi.org/10.3390/cells13070647; https://doi.org/10.3390/cells5010001) (aspenstrom2024mirogtpasesat pages 3-4, tang2015mirogtpasesin pages 6-8, tang2015mirogtpasesin pages 5-6)

2) Recent developments (emphasis 2023–2024)
- MIRO-1–VDAC-1 axis and membrane potential: In C. elegans, MIRO-1 physically interacts with VDAC-1 and is required to sustain mitochondrial membrane potential (ΔΨm). TMRE/mito::GFP imaging (n > 200 mitochondria) and JC-1 assays (n = 3 replicates) show significant ΔΨm reductions upon miro-1 loss or EF-hand mutation; MIRO-1 levels are stochastically elevated on fragmented mitochondria in wounded animals (2023). (EMBO Reports; URL: https://doi.org/10.15252/embr.202256297) (ren2023miro‐1interactswith pages 4-5)
- Transport adaptors and directionality in neurons: A 2024 study in C. elegans neurons demonstrates that MIRO-1 promotes recruitment/enrichment of RIC-7 on mitochondria and optimizes kinesin-1–mediated anterograde transport, while a RIC-7/kinesin-1 pathway can drive residual anterograde movement in miro-1 mutants, indicating partial MIRO-1 independence for anterograde transport. MTX-2 (metaxin-2) helps concentrate RIC-7 at mitochondrial subdomains. (bioRxiv; URL: https://doi.org/10.1101/2023.07.12.548706) (wu2024polarizedlocalizationof pages 14-17)
- Updated mechanistic synthesis: A 2024 review consolidates Miro’s dual GTPase domains, EF-hand calcium sensing, links to TRAK/Milton adaptors and dynein/kinesin motors, and roles at ER–mitochondria contacts and peroxisomes, relevant for interpreting worm MIRO-1 function. (Cells; URL: https://doi.org/10.3390/cells13070647) (aspenstrom2024mirogtpasesat pages 3-4)

3) Functions, pathways, and localization in C. elegans
- Adaptor complexes and motor coupling in vivo
• Metaxin-centered adaptor complexes: MIRO-1 binds MTX-1/MTX-2 and KLC-1, forming adaptor assemblies; MIRO-1 with MTX-2 and TRAK-1 also forms an adaptor complex for dynein-based transport. Genetic and biochemical data in PVD and DA9 neurons support motor-specific adaptor roles, with MIRO-1 acting as an accessory organizer. (Zhao et al., Nat Commun, 2021; URL: https://doi.org/10.1038/s41467-020-20346-2) (zhao2021metaxinsarecore pages 10-10)
• RIC-7 pathway integration: MIRO-1 facilitates RIC-7 mitochondrial recruitment and puncta formation, enhancing kinesin-1 anterograde transport, but is not strictly required for anterograde flux over long timescales. MTX-2 contributes to RIC-7 concentration at leading mitochondrial edges. (Wu et al., 2024; URL: https://doi.org/10.1101/2023.07.12.548706) (wu2024polarizedlocalizationof pages 14-17)
- Directionality and transport regulation
• Anterograde vs retrograde: Worm studies indicate MIRO-1 optimizes anterograde mitochondrial transport via RIC-7/kinesin-1 and participates in dynein-coupled complexes via MTX-2/TRAK-1 for retrograde transport; without MIRO-1, axonal mitochondria become largely immobilized, although some anterograde motion persists through RIC-7/kinesin-1. (Zhao et al., 2021; Wu et al., 2024) (zhao2021metaxinsarecore pages 10-10, wu2024polarizedlocalizationof pages 14-17)
• Ca2+ sensing: EF-hand Ca2+-binding motifs are conserved and functionally implicated in transport regulation across species; in worms, MIRO-1 EF-hand mutation impairs ΔΨm and stress responses, consistent with Ca2+-responsive regulation. (Ren et al., 2023; Aspenström, 2024) (ren2023miro‐1interactswith pages 4-5, aspenstrom2024mirogtpasesat pages 3-4)
- ER–mitochondria contacts and quality control
• ER–mitochondria interfaces: Cross-species data implicate Miro in ER–mitochondria contact regulation; in worms, MIRO-1-dependent mitochondrial relocalization accompanies organismal responses to mitochondrial dysfunction and detoxification programs, consistent with contact/quality-control roles. (Mao et al., Cell Metab, 2019; URL: https://doi.org/10.1016/j.cmet.2019.01.022; Aspenström, 2024) (aspenstrom2024mirogtpasesat pages 3-4)
• Mitophagy/quality control axis: Miro is targeted in PINK1/Parkin pathways to halt motility and promote mitophagy in other models; worm phenotypes (reduced mitochondrial abundance, longevity) are consistent with altered turnover/quality control under miro-1 loss. (Tang, 2015; Shen et al., 2016) (tang2015mirogtpasesin pages 6-8, tang2015mirogtpasesin pages 5-6, shen2016c.elegansmiro1 pages 11-13)
- Outer membrane potential control via VDAC-1
• MIRO-1–VDAC-1 interaction directly sustains ΔΨm and ATP production in vivo; disruption (miro-1 loss/EF-hand mutation) reduces ΔΨm and ATP in worms, linking MIRO-1’s Ca2+ signaling to bioenergetic maintenance. (Ren et al., 2023) (ren2023miro‐1interactswith pages 4-5)

4) Phenotypes and real-world implementations/applications
- Lifespan and mitochondrial abundance: miro-1(tm1966) mutants have approximately half the mitochondrial amount of wild type (~50%) with only mildly reduced oxygen consumption, modestly reduced oxidative damage, weak UPRmt activation, and significant lifespan extension dependent on daf-16/FOXO; simultaneous tissue loss (muscle + neurons) is required for full lifespan extension. (PLoS ONE, 2016; URL: https://doi.org/10.1371/journal.pone.0153233) (shen2016c.elegansmiro1 pages 11-13)
- Neuronal mitochondrial density and transport: MIRO-1 influences mitochondrial numbers in a neuron-specific manner (e.g., increased number in AIY upon miro-1 loss; decreased in DA9 in other studies), and loss of miro-1 largely immobilizes axonal mitochondria, revealing reliance on MIRO-1/MTX/TRAK/RIC-7 transport modules. (bioRxiv, 2024; Nat Commun, 2021; URLs: https://doi.org/10.1101/2023.07.12.548706; https://doi.org/10.1038/s41467-020-20346-2) (wu2024polarizedlocalizationof pages 14-17, zhao2021metaxinsarecore pages 10-10)
- Epidermal wound closure: MIRO-1 is required for rapid, Ca2+-dependent mitochondrial fragmentation after wounding; increasing fragmentation (e.g., in fzo-1 fusion-defective background) accelerates actin-based wound repair via mtROS and cytochrome P450 signaling. (Nat Commun, 2020; URL: https://doi.org/10.1038/s41467-020-14885-x) (ren2023miro‐1interactswith pages 4-5)
- Stress-induced mitochondrial relocalization: Upon mitochondrial dysfunction, C. elegans mobilizes mitochondria in a MIRO-1/TRAK-dependent manner to coordinate metabolic and detoxification gene programs. (Cell Metab, 2019; URL: https://doi.org/10.1016/j.cmet.2019.01.022) (aspenstrom2024mirogtpasesat pages 3-4)
- Translational/expert context: Reviews emphasize Miro as a central node linking transport, Ca2+ homeostasis, and quality control; these processes are tied to neurodegeneration across species, underscoring the utility of the worm MIRO-1 system for dissecting disease mechanisms. (Cells, 2024; Cells, 2015) (aspenstrom2024mirogtpasesat pages 3-4, tang2015mirogtpasesin pages 6-8, tang2015mirogtpasesin pages 5-6)

5) Quantitative data and statistics (selected)
- Mitochondrial amount: ~50% of wild type mitochondrial content in miro-1 mutants by mtDNA and imaging; lifespan extension significant; oxygen consumption only weakly reduced. (PLoS ONE, 2016; URL: https://doi.org/10.1371/journal.pone.0153233) (shen2016c.elegansmiro1 pages 11-13)
- Membrane potential and ATP: TMRE/mito::GFP (n > 200 mitochondria) and JC-1 assays (n = 3) show significant ΔΨm and ATP reductions in miro-1 loss and EF-hand mutants (P < 0.01 to P < 0.001). (EMBO Reports, 2023; URL: https://doi.org/10.15252/embr.202256297) (ren2023miro‐1interactswith pages 4-5)
- RIC-7 recruitment metrics: RIC-7 mitochondrial enrichment is reduced by about 1.3-fold in miro-1 mutants; RIC-7 N-terminus (1–99 aa) colocalizes with ~99% of mitochondria but shows ~10% distal enrichment; 1–470 aa fragment shows ~21% distal enrichment, reflecting MIRO-1’s role in optimizing leading-end concentration. (bioRxiv, 2024; URL: https://doi.org/10.1101/2023.07.12.548706) (wu2024polarizedlocalizationof pages 14-17)
- Biochemical complex assembly: MIRO-1/MTX-1/MTX-2/KLC-1 and MIRO-1/MTX-2/TRAK-1 assemblies detected by gel filtration and pull-down; one IP represented roughly 25% of eluted complex and n = 3 independent experiments. (Nat Commun, 2021; URL: https://doi.org/10.1038/s41467-020-20346-2) (zhao2021metaxinsarecore pages 10-10)

6) Mechanistic interpretation and expert analysis
- Core function in C. elegans: MIRO-1 acts as an outer-membrane adaptor/scaffold that integrates Ca2+ signals (via EF-hands) with motor engagement and bioenergetics control. In neurons, MIRO-1 collaborates with MTX-1/2 and TRAK-1 to couple mitochondria to kinesin-1 and dynein; it also recruits/organizes RIC-7 to optimize anterograde transport. In epidermis and wounded tissues, MIRO-1 mediates Ca2+-dependent mitochondrial fragmentation that accelerates repair. Its interaction with VDAC-1 supports mitochondrial potential and activity. (Ren 2023; Zhao 2021; Wu 2024; Fu 2020) (ren2023miro‐1interactswith pages 4-5, zhao2021metaxinsarecore pages 10-10, wu2024polarizedlocalizationof pages 14-17)
- Quality control coupling: Across species, PINK1/Parkin control Miro degradation to arrest transport and enable mitophagy; worm data (reduced mitochondrial content, altered activity, longevity) are compatible with enhanced turnover/quality control when miro-1 is reduced. (Tang 2015; Shen 2016; Aspenström 2024) (tang2015mirogtpasesin pages 6-8, tang2015mirogtpasesin pages 5-6, shen2016c.elegansmiro1 pages 11-13, aspenstrom2024mirogtpasesat pages 3-4)
- Pathway placement: MIRO-1 integrates signals from Ca2+ influx and ER–mitochondria interfaces to regulate transport and ΔΨm, thereby influencing neuronal function, stress response (wounding), and organismal lifespan.

Embedded evidence table
| Study (first author, year) | Organism / cell type / neuron | Experimental focus | Key findings | Quantitative data (units) | URL (doi link) | Notes |
|---|---|---|---|---:|---|---|
| Ren et al., 2023 (ren2023miro‐1interactswith pages 4-5) | Caenorhabditis elegans (various tissues, isolated mitochondria) | MIRO-1 — VDAC-1 interaction; mitochondrial membrane potential (ΔΨm) | MIRO-1 physically interacts with VDAC-1 and is required to maintain mitochondrial membrane potential and ATP levels; MIRO-1 enriched on fragmented mitochondria after wounding (stress relocalization) | TMRE/mito::GFP imaging: n > 200 mitochondria (normalized TMRE ratio); JC-1 assays on isolated mitochondria: n = 3 biological replicates; significance (P < 0.01, *P < 0.001) | https://doi.org/10.15252/embr.202256297 | Strong biochemical + in vivo ΔΨm evidence implicating MIRO-1 in maintaining mitochondrial activity (ren2023miro‐1interactswith pages 4-5). |
| Fu et al., 2020 (ren2023miro‐1interactswith pages 4-5, aspenstrom2024mirogtpasesat pages 3-4) | C. elegans epidermis (wounding model) | Wound-triggered mitochondrial fragmentation; role of MIRO-1 and Ca2+ in wound repair | Wounding triggers rapid, reversible mitochondrial fragmentation that requires MIRO-1 and cytosolic Ca2+; enhanced fragmentation accelerates actin-based wound closure via mtROS and cytochrome P450 signaling | Fragmentation measurable by confocal imaging; genetic dependence on MIRO-1 and Ca2+ (statistical comparisons reported in paper) | https://doi.org/10.1038/s41467-020-14885-x | Demonstrates MIRO-1 role in stress-induced mitochondrial dynamics and physiological tissue repair (wound closure) (cited with related mechanistic context) (ren2023miro‐1interactswith pages 4-5, aspenstrom2024mirogtpasesat pages 3-4). |
| Zhao et al., 2021 (zhao2021metaxinsarecore pages 10-10) | C. elegans neurons (PVD, DA9) and biochemical fractions | Metaxins (MTX-1/MTX-2) as core components of mitochondrial transport adaptor complexes with MIRO-1 and TRAK-1 | MTX-1/2 bind MIRO-1 and kinesin light chain (KLC-1) to form adaptor complexes; MTX-2, MIRO-1, TRAK-1 form a distinct adaptor for dynein-based transport; MIRO-1 plays accessory role in adaptor assembly and transport specification | Analytical gel-filtration / IP: ~25% of total elution in one assay; experiments repeated (n = 3 independent experiments); neuronal mitochondrial distribution defects and genetic interaction data presented | https://doi.org/10.1038/s41467-020-20346-2 | Provides biochemical and in vivo genetic evidence that MIRO-1 participates in adaptor complexes with metaxins that regulate motor-specific mitochondrial transport (zhao2021metaxinsarecore pages 10-10). |
| Wu et al., 2024 (bioRxiv) (wu2024polarizedlocalizationof pages 14-17) | C. elegans neurons (AIY, DA9) | RIC-7 / kinesin-1 pathway and MIRO-1 contribution to anterograde vs retrograde transport | MIRO-1 promotes recruitment/enrichment of RIC-7 on mitochondria and optimizes kinesin-1–mediated anterograde transport but is not strictly essential; miro mutants show largely immobilized axonal mitochondria yet residual long-timescale anterograde movement depends on RIC-7 + kinesin-1; MTX-2 partially redundant with MIRO-1 for RIC-7 localization | RIC-7 mitochondrial enrichment reduced ~1.3-fold in miro mutants; RIC-7 N-term (1–99 aa) colocalizes with mitochondria ~99% but distal enrichment ~10%; 1–470 aa shows ~21% distal enrichment; other localization metrics reported | https://doi.org/10.1101/2023.07.12.548706 | Supports a model where MIRO-1 helps position adaptor machinery (RIC-7) to promote efficient anterograde transport, while alternative/parallel mechanisms exist (wu2024polarizedlocalizationof pages 14-17). |
| Mao et al., 2019 (aspenstrom2024mirogtpasesat pages 3-4, zhao2021metaxinsarecore pages 10-10) | C. elegans intestinal and other tissues | Mitochondrial relocalization in response to dysfunction; MIRO-1/TRAK involvement | Mitochondrial dysfunction triggers relocalization events that depend on MIRO-1 and TRAK orthologues; relocalization couples to nuclear hormone receptor–dependent detoxification gene activation | Imaging and genetic perturbations show relocalization of mitochondria upon dysfunction (quantitative metrics reported in source) | https://doi.org/10.1016/j.cmet.2019.01.022 | Connects MIRO-1–dependent transport machinery to organismal responses to mitochondrial stress and transcriptional programs (referenced as mechanistic C. elegans evidence) (aspenstrom2024mirogtpasesat pages 3-4, zhao2021metaxinsarecore pages 10-10). |
| Shen et al., 2016 (shen2016c.elegansmiro1 pages 11-13) | C. elegans whole-animal assays (muscle, neurons) | miro-1 loss-of-function phenotypes: mitochondrial content, lifespan, mitochondrial activity markers | miro-1(tm1966) mutants show ~50% of wild-type mitochondrial amount, modestly reduced oxidative damage, weak activation of UPRmt, and extended organismal lifespan dependent on daf-16/FOXO | Mitochondrial amount ≈ 50% of WT (mtDNA copy number / imaging); lifespan extension statistically significant; oxygen consumption only weakly reduced | https://doi.org/10.1371/journal.pone.0153233 | Demonstrates systemic consequences of miro-1 loss on mitochondrial abundance and organismal longevity; suggests altered turnover/quality control (shen2016c.elegansmiro1 pages 11-13). |
| Aspenström review, 2024 (aspenstrom2024mirogtpasesat pages 3-4) | Cross-species review (mammal, fly, worm context) | Miro GTPase domain architecture, EF-hand Ca2+ sensing, PINK1/Parkin regulation, ER–mitochondria contact roles | Summarizes that MIRO proteins have tandem GTPase domains, tandem EF-hand Ca2+-binding motifs, and regulate motor/adaptor interactions and ER–mitochondria contacts; Ca2+ binding can arrest transport and MIRO is targeted by PINK1/Parkin during mitophagy | Review synthesizing structural/functional data across models; highlights nGTPase as primary regulatory domain and EF-hands as Ca2+-sensors | https://doi.org/10.3390/cells13070647 | Provides mechanistic framework and up-to-date (2024) context for interpreting C. elegans MIRO-1 experimental results (aspenstrom2024mirogtpasesat pages 3-4). |

Table: Concise evidence table summarizing key C. elegans studies and a recent review on MIRO-1 (miro-1/K08F11.5), listing experimental focus, main findings, quantitative metrics, DOIs and notes; useful as a quick reference linking worm-specific data to mechanistic context.

Ambiguity check and caveats
- Gene symbol verification: “miro-1” in this report strictly refers to C. elegans K08F11.5 (UniProt Q94263), not to mammalian RHOT1 or other organisms’ Miro proteins; cross-species insights are used only to interpret worm results. (Shen 2016; Aspenström 2024) (shen2016c.elegansmiro1 pages 11-13, aspenstrom2024mirogtpasesat pages 3-4)
- Preprints: Some 2024 transport data are from a bioRxiv preprint and should be interpreted accordingly until peer review. (Wu 2024) (wu2024polarizedlocalizationof pages 14-17)

References (with URLs and dates)
- Shen Y. et al., 2016, PLoS ONE. C. elegans miro-1 mutation reduces mitochondria and extends lifespan. URL: https://doi.org/10.1371/journal.pone.0153233 (Apr 2016). (shen2016c.elegansmiro1 pages 11-13)
- Ren X. et al., 2023, EMBO Reports. MIRO-1 interacts with VDAC-1 to regulate mitochondrial membrane potential in C. elegans. URL: https://doi.org/10.15252/embr.202256297 (Jun 2023). (ren2023miro‐1interactswith pages 4-5)
- Wu Y. et al., 2024, bioRxiv. Polarized localization of kinesin-1 and RIC-7 drives axonal mitochondria anterograde transport. URL: https://doi.org/10.1101/2023.07.12.548706 (Jul 2024). (wu2024polarizedlocalizationof pages 14-17)
- Zhao Y. et al., 2021, Nature Communications. Metaxins are core components of mitochondrial transport adaptor complexes. URL: https://doi.org/10.1038/s41467-020-20346-2 (Jan 2021). (zhao2021metaxinsarecore pages 10-10)
- Mao K. et al., 2019, Cell Metabolism. Mitochondrial dysfunction in C. elegans activates mitochondrial relocalization and detoxification genes. URL: https://doi.org/10.1016/j.cmet.2019.01.022 (May 2019). (aspenstrom2024mirogtpasesat pages 3-4)
- Fu H. et al., 2020, Nature Communications. Wounding triggers MIRO-1–dependent mitochondrial fragmentation to accelerate wound closure. URL: https://doi.org/10.1038/s41467-020-14885-x (Feb 2020). (ren2023miro‐1interactswith pages 4-5)
- Aspenström P., 2024, Cells. Miro GTPases at the crossroads of cytoskeletal dynamics and mitochondrial trafficking (review). URL: https://doi.org/10.3390/cells13070647 (Apr 2024). (aspenstrom2024mirogtpasesat pages 3-4)
- Tang B., 2015, Cells. MIRO GTPases in mitochondrial transport, homeostasis and pathology (review). URL: https://doi.org/10.3390/cells5010001 (Dec 2015). (tang2015mirogtpasesin pages 6-8, tang2015mirogtpasesin pages 5-6)

References

1. (shen2016c.elegansmiro1 pages 11-13): Yanqing Shen, Li Fang Ng, Natarie Pei Wen Low, Thilo Hagen, Jan Gruber, and Takao Inoue. C. elegans miro-1 mutation reduces the amount of mitochondria and extends life span. PLoS ONE, 11:e0153233, Apr 2016. URL: https://doi.org/10.1371/journal.pone.0153233, doi:10.1371/journal.pone.0153233. This article has 24 citations and is from a peer-reviewed journal.

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4. (tang2015mirogtpasesin pages 6-8): Bor Tang. Miro gtpases in mitochondrial transport, homeostasis and pathology. Cells, 5:1, Dec 2015. URL: https://doi.org/10.3390/cells5010001, doi:10.3390/cells5010001. This article has 81 citations and is from a poor quality or predatory journal.

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Citations

1. wu2024polarizedlocalizationof pages 14-17
2. aspenstrom2024mirogtpasesat pages 3-4
3. zhao2021metaxinsarecore pages 10-10
4. tang2015mirogtpasesin pages 6-8
5. tang2015mirogtpasesin pages 5-6
6. https://doi.org/10.1371/journal.pone.0153233
7. https://doi.org/10.3390/cells13070647
8. https://doi.org/10.15252/embr.202256297
9. https://doi.org/10.3390/cells13070647;
10. https://doi.org/10.3390/cells5010001
11. https://doi.org/10.1101/2023.07.12.548706
12. https://doi.org/10.1038/s41467-020-20346-2
13. https://doi.org/10.1016/j.cmet.2019.01.022;
14. https://doi.org/10.1101/2023.07.12.548706;
15. https://doi.org/10.1038/s41467-020-14885-x
16. https://doi.org/10.1016/j.cmet.2019.01.022
17. https://doi.org/10.1371/journal.pone.0153233,
18. https://doi.org/10.3390/cells13070647,
19. https://doi.org/10.15252/embr.202256297,
20. https://doi.org/10.3390/cells5010001,
21. https://doi.org/10.1101/2023.07.12.548706,
22. https://doi.org/10.1038/s41467-020-20346-2,