id: Q9BXK5
gene_symbol: BCL2L13
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 'BCL2L13 (Bcl-rambo, Mil1) is a tail-anchored mitochondrial outer-membrane protein of the BCL-2 family that contains all four BCL-2 homology motifs (BH1-BH4) plus a unique ~250-residue insertion with tandem repeats preceding its C-terminal transmembrane anchor. It is the mammalian functional homolog of the yeast mitophagy receptor Atg32: through an LC3-interacting region it binds Atg8-family proteins (LC3/GABARAP, including GABARAPL2) to recruit the autophagy machinery to mitochondria, promoting mitochondrial fragmentation and selective autophagy of mitochondria (mitophagy) independently of the canonical DRP1 fission machinery. BCL2L13 was originally described as a pro-apoptotic BCL-2 homolog whose cell-death activity, which can promote caspase-3 activation, is conferred by its membrane-anchored C-terminal region rather than its BH motifs; unlike most BCL-2-family members it does not heterodimerize with other family members. It is broadly expressed (notably in heart, placenta, pancreas and skeletal muscle) and is targeted by the Legionella pneumophila effector SidF, which neutralizes it to block host apoptosis. A short nuclear-localized splice isoform lacking the transmembrane anchor also exists.'
alternative_products:
- name: '2'
  id: Q9BXK5-1
- name: '1'
  id: Q9BXK5-2
  sequence_note: VSP_000526, VSP_000527
- name: '3'
  id: Q9BXK5-4
  sequence_note: VSP_046931
existing_annotations:
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: BCL2L13 is a mitochondrial protein that acts at the mitochondrion (mitophagy receptor and pro-apoptotic activity at the mitochondrial outer membrane).
    action: ACCEPT
    reason: Mitochondrial localization/activity is strongly and consistently supported; the mitochondrion is the principal functional compartment.
    supported_by:
    - reference_id: PMID:11262395
      supporting_text: Bcl-rambo was localized to mitochondria
      reference_section_type: ABSTRACT
    - reference_id: file:human/BCL2L13/BCL2L13-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion membrane'
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: BCL2L13 is a single-pass tail-anchored membrane protein; generic membrane localization is correct but uninformative relative to the specific mitochondrial membrane.
    action: MARK_AS_OVER_ANNOTATED
    reason: The generic membrane term is subsumed by the more specific and well-supported mitochondrial (outer) membrane localization.
    supported_by:
    - reference_id: file:human/BCL2L13/BCL2L13-uniprot.txt
      supporting_text: Single-pass membrane protein
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: A nuclear localization is reported in UniProt, largely for the truncated isoform 1 that lacks the transmembrane anchor; it is secondary to the mitochondrial role.
    action: KEEP_AS_NON_CORE
    reason: Nuclear localization is documented (especially for the short nuclear isoform) but is not the functional compartment for the conserved mitophagy/mitochondrial activities.
    supported_by:
    - reference_id: file:human/BCL2L13/BCL2L13-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: [Isoform 1]: Nucleus'
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: BCL2L13/Bcl-rambo can promote apoptosis (originally described as a pro-apoptotic BCL-2 homolog), an InterPro-based transfer consistent with the experimental literature.
    action: KEEP_AS_NON_CORE
    reason: A pro-apoptotic capacity is genuine but context/overexpression-dependent and secondary to the conserved mitophagy-receptor function.
    supported_by:
    - reference_id: PMID:11262395
      supporting_text: its overexpression induces apoptosis that is specifically blocked by the caspase inhibitors, IAPs
      reference_section_type: ABSTRACT
- term:
    id: GO:0031966
    label: mitochondrial membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: BCL2L13 is anchored in the mitochondrial membrane (outer membrane), consistent with its tail-anchor and UniProt subcellular location.
    action: ACCEPT
    reason: Well-supported core localization; the mitochondrial membrane is where BCL2L13 acts.
    supported_by:
    - reference_id: file:human/BCL2L13/BCL2L13-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: [Isoform 2]: Mitochondrion membrane'
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0042981
    label: regulation of apoptotic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: As a BCL-2-family protein with pro-apoptotic activity, BCL2L13 participates in regulation of apoptosis; an InterPro-based transfer consistent with the literature.
    action: KEEP_AS_NON_CORE
    reason: Supported by the apoptosis literature but context-dependent and secondary to the mitophagy-receptor function.
    supported_by:
    - reference_id: PMID:11262395
      supporting_text: Bcl-rambo constitutes a novel type of pro-apoptotic Bcl-2 member that triggers cell death independently of its BH motifs.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16189514
  qualifier: enables
  review:
    summary: High-throughput interactome protein-binding annotation; uninformative for BCL2L13 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from a proteome-scale interaction map does not identify an interpretable BCL2L13 function.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17360363
  qualifier: enables
  review:
    summary: This protein-binding annotation reflects the specific interaction of Bcl-rambo with the Legionella effector SidF (which neutralizes it to block host apoptosis); as bare protein binding it is uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: The underlying SidF interaction is meaningful and confirms Bcl-rambo as a pro-death host target, but the generic protein binding term does not capture this; no specific GO binding term for a bacterial effector applies.
    supported_by:
    - reference_id: PMID:17360363
      supporting_text: SidF contributes to apoptosis resistance in L. pneumophila-infected cells by specifically interacting with and neutralizing the effects of BNIP3 and Bcl-rambo, two proapoptotic members of Bcl2 protein family.
      reference_section_type: ABSTRACT
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: High-throughput interactome protein-binding annotation; uninformative for BCL2L13 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from a proteome-scale interactome map is not functionally specific.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25910212
  qualifier: enables
  review:
    summary: High-throughput interactome protein-binding annotation; uninformative for BCL2L13 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from a disease-interactome perturbation study is not functionally specific.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26871637
  qualifier: enables
  review:
    summary: High-throughput alternative-splicing interactome protein-binding annotation; uninformative for BCL2L13 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from a large-scale splicing-interactome study is not functionally specific.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: High-throughput interactome protein-binding annotation; uninformative for BCL2L13 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from a large-scale interactome study is not functionally specific.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: High-throughput interactome protein-binding annotation; uninformative for BCL2L13 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from a reference binary interactome map is not functionally specific.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: High-throughput neurodegenerative-disease interactome protein-binding annotation; uninformative for BCL2L13 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from a disease-interactome study is not functionally specific.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: High-throughput interactome protein-binding annotation; uninformative for BCL2L13 function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic protein binding from a cell-specific interactome remodeling study is not functionally specific.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: is_active_in
  review:
    summary: Orthology-based transfer of mitochondrial activity, consistent with the well-supported mitochondrial localization/function of BCL2L13.
    action: ACCEPT
    reason: Consistent with the core mitochondrial compartment where BCL2L13 acts.
    supported_by:
    - reference_id: PMID:11262395
      supporting_text: Bcl-rambo was localized to mitochondria
      reference_section_type: ABSTRACT
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Immunofluorescence-based mitochondrial localization, consistent with the literature.
    action: ACCEPT
    reason: Directly supported core localization.
    supported_by:
    - reference_id: PMID:11262395
      supporting_text: Bcl-rambo was localized to mitochondria
      reference_section_type: ABSTRACT
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HTP
  original_reference_id: PMID:34800366
  qualifier: located_in
  review:
    summary: High-throughput mitochondrial proteome localization, consistent with BCL2L13 being a mitochondrial protein.
    action: ACCEPT
    reason: Consistent with the well-supported core mitochondrial localization.
    supported_by:
    - reference_id: PMID:34800366
      supporting_text: mitochondrial proteome
      reference_section_type: TITLE
- term:
    id: GO:0006915
    label: apoptotic process
  evidence_type: NAS
  original_reference_id: PMID:11262395
  qualifier: involved_in
  review:
    summary: The founding Bcl-rambo study reports that overexpression induces caspase-dependent apoptosis, providing the basis for the apoptotic-process annotation.
    action: KEEP_AS_NON_CORE
    reason: A pro-apoptotic role is supported but is overexpression-driven and context-dependent; secondary to the conserved mitophagy-receptor function.
    supported_by:
    - reference_id: PMID:11262395
      supporting_text: its overexpression induces apoptosis that is specifically blocked by the caspase inhibitors, IAPs
      reference_section_type: ABSTRACT
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: NAS
  original_reference_id: PMID:11262395
  qualifier: located_in
  review:
    summary: The founding study localized Bcl-rambo to mitochondria.
    action: ACCEPT
    reason: Directly supported core localization.
    supported_by:
    - reference_id: PMID:11262395
      supporting_text: Bcl-rambo was localized to mitochondria
      reference_section_type: ABSTRACT
- term:
    id: GO:0008656
    label: cysteine-type endopeptidase activator activity involved in apoptotic process
  evidence_type: NAS
  original_reference_id: PMID:11262395
  qualifier: enables
  review:
    summary: BCL2L13-induced apoptosis is caspase-dependent (blocked by caspase inhibitors/IAPs), and UniProt states it may promote caspase-3 activation; this caspase-activator annotation captures a contextual pro-apoptotic effect rather than a direct, conserved molecular function.
    action: KEEP_AS_NON_CORE
    reason: The caspase-3 activation is indirect/context-dependent (overexpression-driven apoptosis) and is not the conserved core molecular function (mitophagy-receptor activity); retained as a non-core apoptosis-related annotation.
    supported_by:
    - reference_id: PMID:11262395
      supporting_text: its overexpression induces apoptosis that is specifically blocked by the caspase inhibitors, IAPs
      reference_section_type: ABSTRACT
    - reference_id: file:human/BCL2L13/BCL2L13-uniprot.txt
      supporting_text: May promote the activation of caspase-3 and apoptosis.
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:11262395
  qualifier: located_in
  review:
    summary: Bcl-rambo's cell-death activity maps to its membrane-anchored C-terminal domain; generic membrane localization is correct but uninformative.
    action: MARK_AS_OVER_ANNOTATED
    reason: Subsumed by the specific mitochondrial (outer) membrane localization.
    supported_by:
    - reference_id: PMID:11262395
      supporting_text: the Bcl-rambo cell death activity was induced by its membrane-anchored C-terminal domain
      reference_section_type: ABSTRACT
- term:
    id: GO:0140580
    label: mitochondrion autophagosome adaptor activity
  evidence_type: IDA
  original_reference_id: PMID:26146385
  qualifier: enables
  review:
    summary: BCL2L13/Bcl2-L-13 is an outer-mitochondrial-membrane mitophagy receptor that binds LC3 through its WXXI/LIR motif and recruits autophagy machinery to mitochondria.
    action: NEW
    reason: The PN-guided review identified that the YAML's proposed "mitophagy receptor activity" request is already covered by GO:0140580. This existing MF should be added instead of requesting a new term.
    supported_by:
    - reference_id: PMID:26146385
      supporting_text: Bcl2-L-13 binds to LC3 through the WXXI motif and induces mitochondrial fragmentation and mitophagy
      reference_section_type: ABSTRACT
- term:
    id: GO:0000423
    label: mitophagy
  evidence_type: IMP
  original_reference_id: PMID:26146385
  qualifier: involved_in
  review:
    summary: BCL2L13 promotes selective autophagy of mitochondria, and knockdown attenuates damage-induced mitochondrial fragmentation and mitophagy.
    action: NEW
    reason: The review already treats mitophagy as the core biological process, but the seeded existing_annotations lacked a manual recommendation for the BP term. This adds the existing GO process term with primary evidence.
    supported_by:
    - reference_id: PMID:26146385
      supporting_text: Knockdown of Bcl2-L-13 attenuates mitochondrial damage-induced fragmentation and mitophagy
      reference_section_type: ABSTRACT
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  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:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: PMID:11262395
  title: Bcl-rambo, a novel Bcl-2 homologue that induces apoptosis via its unique
    C-terminal extension.
  findings: []
- id: PMID:16189514
  title: Towards a proteome-scale map of the human protein-protein interaction network.
  findings: []
- id: PMID:17360363
  title: Legionella pneumophila inhibits macrophage apoptosis by targeting pro-death
    members of the Bcl2 protein family.
  findings: []
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:25910212
  title: Widespread macromolecular interaction perturbations in human genetic disorders.
  findings: []
- id: PMID:26871637
  title: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins
    and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:34800366
  title: Quantitative high-confidence human mitochondrial proteome and its dynamics
    in cellular context.
  findings: []
- id: PMID:26146385
  title: Bcl-2-like protein 13 is a mammalian Atg32 homologue that mediates mitophagy
    and mitochondrial fragmentation.
  full_text_unavailable: true
  findings:
  - statement: BCL2L13 is the mammalian functional homolog of yeast Atg32; it binds
      LC3 through a WXXI/LIR motif and induces both mitochondrial fragmentation and
      mitophagy. The BH domains mediate fragmentation while the WXXI motif facilitates
      mitophagy.
  - statement: BCL2L13 induces mitochondrial fragmentation in the absence of DRP1/DNM1L
      and induces mitophagy in Parkin-deficient cells, placing it in a ubiquitin-independent,
      Parkin-independent receptor-mediated mitophagy pathway, and it can rescue mitophagy
      in Atg32-deficient yeast.
- id: PMID:36589739
  title: Biological properties of the BCL-2 family protein BCL-RAMBO, which regulates
    apoptosis, mitochondrial fragmentation, and mitophagy.
  full_text_unavailable: true
  findings:
  - statement: BCL-RAMBO/BCL2L13 is an integral mitochondrial outer-membrane protein
      with BH1-BH4 domains, a BHNo region containing the LC3-interacting region (human
      LIR WQQI), and a C-terminal transmembrane anchor; it functions as a mitophagy
      receptor recruiting ATG8-family proteins (LC3/GABARAP) via the LIR motif.
  - statement: Phosphorylation near the LIR (Ser272 in mouse numbering) tunes LC3
      binding and mitophagic activity; PGAM5 acts as a negative regulator by dephosphorylating
      BCL2L13, and BCL2L13 is reported to recruit the ULK1 complex to the mitochondrial
      outer membrane to initiate mitophagy.
- id: PMID:39175772
  title: BCL2L13 at endoplasmic reticulum-mitochondria contact sites regulates calcium
    homeostasis to maintain skeletal muscle function.
  full_text_unavailable: true
  findings:
  - statement: BCL2L13 localizes to mitochondria, ER, and mitochondria-associated
      membranes (ER-mitochondria contact sites) and regulates ER-mitochondria calcium
      homeostasis; its knockdown alters cytosolic calcium release and mitochondrial
      calcium uptake without changing the number of ER-mitochondria contact sites,
      indicating a functional rather than structural contact-site role.
  - statement: Loss of Bcl2l13 in zebrafish impairs skeletal muscle structure and
      function and decreases mitochondrial complex activity, supporting a physiological
      role in muscle bioenergetics and calcium handling.
- id: PMID:37660127
  title: BCL2L13 promotes mitophagy through DNM1L-mediated mitochondrial fission in
    glioblastoma.
  full_text_unavailable: true
  findings:
  - statement: In glioblastoma, BCL2L13 is upregulated and promotes mitochondrial
      fission and high mitophagy flux by targeting DNM1L (DRP1) at the Ser616 site,
      promoting tumor proliferation and invasion; this DNM1L-dependent mechanism is
      context-specific and contrasts with DRP1-independent fragmentation reported elsewhere.
- id: PMID:38494498
  title: YME1L-mediated mitophagy protects renal tubular cells against cellular senescence
    under diabetic conditions.
  full_text_unavailable: true
  findings:
  - statement: BCL2L13 was identified by LC-MS/MS as an interacting partner of the
      inner mitochondrial membrane protease YME1L; YME1L promotes phosphorylation
      of BCL2L13, strengthening BCL2L13-LC3 binding and enhancing mitophagy to restrain
      renal tubular epithelial cell senescence in diabetic kidney disease models.
- id: PMID:34193180
  title: Down-regulation of BCL2L13 renders poor prognosis in clear cell and papillary
    renal cell carcinoma.
  full_text_unavailable: true
  findings:
  - statement: BCL2L13 expression is decreased in clear-cell and papillary renal cell
      carcinoma and lower expression correlates with poorer prognosis independently
      of tumor grade; BCL2L13 positively correlates with SLC25A4 (ANT), implicated
      as a downstream effector in its pro-apoptotic pathway.
- id: file:human/BCL2L13/BCL2L13-uniprot.txt
  title: BCL2L13 (Bcl-rambo) UniProtKB record Q9BXK5
  findings: []
- id: file:human/BCL2L13/BCL2L13-notes.md
  title: Manual BCL2L13 curation notes
  findings: []
core_functions:
- description: BCL2L13/Bcl-rambo functions as a mitophagy receptor at the mitochondrial outer membrane. As the mammalian functional homolog of yeast Atg32, it binds Atg8-family proteins (LC3/GABARAP, including GABARAPL2) via an LC3-interacting region to recruit autophagy machinery to mitochondria, promoting mitochondrial fragmentation and selective autophagy of mitochondria.
  molecular_function:
    id: GO:0140580
    label: mitochondrion autophagosome adaptor activity
  directly_involved_in:
  - id: GO:0000423
    label: mitophagy
  locations:
  - id: GO:0031966
    label: mitochondrial membrane
  supported_by:
  - reference_id: file:human/BCL2L13/BCL2L13-uniprot.txt
    supporting_text: 'Q9BXK5; P60520: GABARAPL2; NbExp=4; IntAct=EBI-747430, EBI-720116;'
    reference_section_type: DATABASE_ENTRY
  - reference_id: file:human/BCL2L13/BCL2L13-uniprot.txt
    supporting_text: GO:0000423; P:mitophagy; IEA:Ensembl.
    reference_section_type: DATABASE_ENTRY
- description: BCL2L13 has a context-dependent pro-apoptotic activity. Originally characterized as a BCL-2 homolog whose overexpression induces caspase-dependent apoptosis via its membrane-anchored C-terminal region (not its BH motifs), it can promote caspase-3 activation and does not heterodimerize with other BCL-2-family members; it is a target of the Legionella effector SidF.
  directly_involved_in:
  - id: GO:0006915
    label: apoptotic process
  locations:
  - id: GO:0031966
    label: mitochondrial membrane
  supported_by:
  - reference_id: PMID:11262395
    supporting_text: its overexpression induces apoptosis that is specifically blocked by the caspase inhibitors, IAPs
    reference_section_type: ABSTRACT
  - reference_id: PMID:11262395
    supporting_text: the Bcl-rambo cell death activity was induced by its membrane-anchored C-terminal domain
    reference_section_type: ABSTRACT
proposed_new_terms: []
suggested_questions:
- question: In normal physiology, is BCL2L13's predominant role the Atg32-like mitophagy-receptor function, the pro-apoptotic function, or are these separable activities engaged in different cell types or stress conditions?
  experts:
  - Murakawa T
  - Otsu K
- question: Does BCL2L13-mediated mitochondrial fragmentation occur independently of the canonical DRP1 fission machinery, and how is the LIR-dependent LC3 binding regulated?
  experts:
  - Murakawa T
  - Otsu K
- question: Is BCL2L13's localization to ER-mitochondria contact sites (mitochondria-associated membranes) and its regulation of ER-mitochondria Ca2+ flux a distinct function from its mitophagy-receptor activity, or are the two mechanistically coupled?
  experts:
  - Amati F
  - Grepper D
- question: How is the choice between DRP1-independent fragmentation (Murakawa) and DNM1L/DRP1-Ser616-dependent fission (glioblastoma) determined, and which cellular contexts favor each, given the opposing tissue-dependent roles of BCL2L13 (pro-survival in GBM vs tumor-suppressive in renal cell carcinoma)?
suggested_experiments:
- hypothesis: BCL2L13 acts as an LIR-dependent mitophagy receptor that recruits LC3/GABARAP to mitochondria to drive their selective autophagy.
  description: Compare wild-type BCL2L13 with LIR-motif point mutants for LC3/GABARAP co-immunoprecipitation and for the ability to induce mitochondrial fragmentation and mitophagy (mito-Keima/mito-QC flux) in BCL2L13-null cells, including under uncoupler-induced and starvation-induced conditions.
  experiment_type: structure-function rescue and mitophagy flux assay
- hypothesis: The pro-apoptotic and mitophagy-receptor activities of BCL2L13 are mechanistically separable.
  description: Use domain-deletion and point-mutant constructs (BH motifs, LIR motif, C-terminal insertion/TM) to dissociate caspase-3 activation/apoptosis from LC3-dependent mitophagy, measuring both readouts in parallel in defined cell models.
  experiment_type: domain dissection with parallel apoptosis and mitophagy readouts