id: P41977
gene_symbol: sod-3
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:6239
  label: Caenorhabditis elegans
description: >-
  sod-3 encodes a mitochondrial matrix manganese superoxide dismutase (MnSOD) of
  Caenorhabditis elegans. The nuclear-encoded 218-residue precursor carries an
  N-terminal mitochondrial transit peptide that directs import into the
  mitochondrial matrix, where the mature chain adopts the characteristic
  iron/manganese superoxide dismutase fold and binds one catalytic Mn(2+) ion per
  subunit. The enzyme dismutates the superoxide anion radical, a by-product of the
  respiratory electron transport chain, into hydrogen peroxide and molecular oxygen
  (2 superoxide + 2 H+ -> H2O2 + O2; EC 1.15.1.1), providing antioxidant defense
  within the organelle. SOD-3 is the paralog of the constitutive, quantitatively
  dominant mitochondrial MnSOD SOD-2, to which it is ~86% identical; unlike sod-2,
  sod-3 is expressed at very low basal levels and is strongly induced by the
  DAF-16/FOXO branch of insulin/IGF-1 signalling, making it a canonical DAF-16 target
  gene and a widely used transcriptional reporter of insulin/IGF-1 pathway activity
  and stress. Basal expression is seen in the pharynx and rectum, expanding to vulva,
  body-wall muscle and hypodermis upon thermal stress. Like SOD-2, SOD-3 physically
  associates with the mitochondrial respiratory supercomplex I:III:IV, positioning it
  to scavenge superoxide near its site of production, and it may help stabilize or
  locally protect the supercomplex, particularly when SOD-2 is absent. Loss of sod-3
  alone does not alter lifespan or the activity of the respiratory complexes, but
  sod-3 shows distinct, non-redundant genetic interactions with electron-transport-chain
  mutants compared with sod-2.
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:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:9353332
  title: Cloning, expression, and characterization of two manganese superoxide dismutases
    from Caenorhabditis elegans.
  findings:
  - statement: >-
      Cloned sod-2 and sod-3, showed both encode mitochondrial (transit-peptide
      bearing) manganese-type superoxide dismutases (~86% identical proteins), and
      directly measured their enzymatic activity after heterologous expression of the
      mature chains in SOD-deficient E. coli (Mn-type: insensitive to hydrogen
      peroxide and cyanide; dimeric; protective against methyl-viologen/paraquat
      oxidative stress). Both proteins were assayed, so the biochemical evidence is
      sod-3-specific as well as sod-2-specific.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Abstract-only in cache (full_text_available: false), but the abstract explicitly
      reports the direct biochemical characterization of BOTH MnSODs, underlying the
      WormBase IDA (superoxide dismutase activity) and IMP (removal of superoxide
      radicals) annotations for sod-3. The IMP is heterologous E. coli complementation,
      not a worm sod-3 mutant phenotype.
- id: PMID:23895727
  title: Novel interactions between mitochondrial superoxide dismutases and the electron
    transport chain.
  findings:
  - statement: >-
      SOD-3 (like SOD-2) localizes to the mitochondrial respiratory supercomplex
      I:III:IV by blue-native gel Western. In contrast to sod-2, loss of sod-3 does
      not decrease complex I-dependent respiration and sod-3 BNGs are normal; sod-3
      single-mutant lifespan equals wild type, but sod-3 has distinct, non-redundant
      genetic interactions with the ETC mutants gas-1, mev-1 and isp-1. sod-3 is an
      mtSOD normally expressed at very low levels and induced by DAF-16.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Full text cached (PMC3838459). The richest sod-3-specific source: directly
      supports the IDA supercomplex localization, the low-basal/DAF-16-inducible
      expression framing, the normal single-mutant lifespan, and the sod-2/sod-3
      non-redundancy. The anti-SOD-2 antibody cross-reacts with SOD-3 (Figure S2), but
      the authors explicitly conclude SOD-3 is localized to the supercomplex.
- id: PMID:17894411
  title: 'The MAP kinase JNK-1 of Caenorhabditis elegans: location, activation, and
    influences over temperature-dependent insulin-like signaling, stress responses,
    and fitness.'
  findings:
  - statement: >-
      Establishes sod-3 as a DAF-16 target gene whose peripheral, non-neuronal
      expression is promoted by JNK-1-driven nuclear translocation of DAF-16. UniProt
      cites this paper for the SUBCELLULAR LOCATION (mitochondrion), TISSUE
      SPECIFICITY (pharynx/rectum basally; vulva, body-wall muscle, hypodermis on
      thermal stress), and heat INDUCTION of SOD-3.
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Abstract-only in cache; the abstract supports the DAF-16-target/sod-3-reporter
      role verbatim. The mitochondrial localization it is cited for by UniProt is in
      the full text (not the abstract), so no verbatim mitochondrial-localization quote
      is available here; mitochondrial localization of this MnSOD is biologically
      unambiguous and concordant with the transit peptide.
existing_annotations:
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetic (IBA) inference that SOD-3 is active in the mitochondrion. Correct
      but less specific than the mitochondrial matrix, where this MnSOD acts.
    action: KEEP_AS_NON_CORE
    reason: >-
      Consistent with the N-terminal mitochondrial transit peptide and with
      experimental localization, but generic relative to mitochondrial matrix
      (GO:0005759), which is retained as the core location. Kept as a correct,
      less-specific companion term.
- term:
    id: GO:0004784
    label: superoxide dismutase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Phylogenetic (IBA) inference of superoxide dismutase activity. This is the core
      molecular function of SOD-3 and is directly confirmed experimentally.
    action: ACCEPT
    reason: >-
      SOD-3 is an experimentally validated manganese superoxide dismutase; the IBA
      call is fully concordant with the IDA evidence (PMID:9353332, in which the SOD-3
      protein was expressed and assayed) and with the Fe/Mn-SOD family assignment.
      Core function.
    supported_by:
    - reference_id: PMID:9353332
      supporting_text: >-
        The expressed enzymes, which were not inhibited by hydrogen peroxide or
        cyanide, are dimeric, show quite different electrophoretic mobilities and
        isoelectric points, but exhibit comparable specific activities.
- term:
    id: GO:0030145
    label: manganese ion binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Phylogenetic (IBA) inference of manganese ion binding, the catalytic cofactor of
      this MnSOD. Concordant with the UniProt Mn(2+) cofactor and Mn-ligand residues
      (His50, His98, Asp179, His183) and with the enzyme's Mn-type biochemistry.
    action: ACCEPT
    reason: >-
      Correct and specific metal-binding function: this is a Mn-type (not Fe- or
      Cu/Zn-type) SOD, insensitive to hydrogen peroxide and cyanide, binding one Mn(2+)
      per subunit. Core cofactor-binding function.
    supported_by:
    - reference_id: PMID:9353332
      supporting_text: >-
        The expressed enzymes, which were not inhibited by hydrogen peroxide or
        cyanide, are dimeric, show quite different electrophoretic mobilities and
        isoelectric points, but exhibit comparable specific activities.
- term:
    id: GO:0004784
    label: superoxide dismutase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Electronic (IEA) assignment of superoxide dismutase activity from combined
      automated methods (ARBA/InterPro/EC/RHEA mapping). Redundant with the
      experimental IDA and phylogenetic IBA calls for the same core function.
    action: ACCEPT
    reason: >-
      Same core molecular function as the IDA/IBA annotations; the EC 1.15.1.1 /
      RHEA:20696 mapping is correct for this enzyme. Retained as concordant supporting
      evidence.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Electronic (UniProt SubCell) mitochondrial localization, matching the UniProt
      subcellular location and the N-terminal mitochondrial transit peptide. Correct
      but generic relative to the mitochondrial matrix, the specific site of action.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct localization but less specific than mitochondrial matrix (GO:0005759),
      which is retained as the core location for this matrix MnSOD. Kept as a correct,
      less-specific companion.
    supported_by:
    - reference_id: PMID:9353332
      supporting_text: >-
        Both deduced protein sequences contain the expected N-terminal mitochondrial
        transit peptides.
- term:
    id: GO:0006801
    label: superoxide metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      Electronic (InterPro2GO) assignment to the general superoxide metabolic process.
      Correct but less specific than removal of superoxide radicals (GO:0019430), which
      is the experimentally supported process.
    action: KEEP_AS_NON_CORE
    reason: >-
      Accurate parent process, but subsumed by the more specific removal of superoxide
      radicals term retained as core. Kept as a correct, less-informative companion.
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Electronic (InterPro2GO) generic metal-ion-binding annotation. Subsumed by the
      specific manganese ion binding (GO:0030145) term.
    action: KEEP_AS_NON_CORE
    reason: >-
      Correct but uninformative parent of manganese ion binding; the specific Mn(2+)
      term is retained as core. Kept as a non-core, less-specific companion.
- term:
    id: GO:0098803
    label: respiratory chain complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: part_of
  review:
    summary: >-
      Electronic (ARBA) assertion that SOD-3 is part_of the respiratory chain complex.
      SOD-3 is a soluble matrix MnSOD that physically associates with supercomplex
      I:III:IV (see the experimental located_in annotation), but it is not a canonical
      structural subunit of an electron-transport complex, so the part_of qualifier
      overstates the relationship.
    action: KEEP_AS_NON_CORE
    reason: >-
      The experimentally supported relationship is association/co-localization with the
      I:III:IV supercomplex (PMID:23895727, located_in), consistent with local
      superoxide scavenging and possible supercomplex stabilization; SOD-3 does not
      carry out or structurally constitute electron transport. The automated part_of
      qualifier is an over-generalization, so this is retained only as a non-core
      companion to the experimental located_in annotation rather than as evidence of
      structural subunit membership.
    supported_by:
    - reference_id: PMID:23895727
      supporting_text: >-
        In addition, the results show that SOD-3 is also localized to the I:III:IV
        supercomplex.
- term:
    id: GO:0098803
    label: respiratory chain complex
  evidence_type: IDA
  original_reference_id: PMID:23895727
  qualifier: part_of
  review:
    summary: >-
      Direct assay (IDA) showing SOD-3 co-localizes with the mitochondrial supercomplex
      I:III:IV by blue-native gel Western blotting. A genuine, sod-3-specific
      localization finding, but a peripheral association rather than the enzyme's core
      identity; the part_of qualifier overstates it (SOD-3 is not a structural ETC
      subunit).
    action: KEEP_AS_NON_CORE
    reason: >-
      Experimentally supported association of SOD-3 with the I:III:IV supercomplex,
      consistent with local scavenging of superoxide at its site of production and a
      possible supercomplex-stabilizing role (the authors note SOD-3 may substitute for
      this SOD-2 function when SOD-2 is absent). Retained as a real but non-core
      localization; SOD-3's core identity is a matrix MnSOD, not a structural ETC
      subunit.
    supported_by:
    - reference_id: PMID:23895727
      supporting_text: >-
        In addition, the results show that SOD-3 is also localized to the I:III:IV
        supercomplex.
- term:
    id: GO:0004784
    label: superoxide dismutase activity
  evidence_type: IDA
  original_reference_id: PMID:9353332
  qualifier: enables
  review:
    summary: >-
      Direct assay (IDA) of superoxide dismutase activity: the mature SOD-3 protein was
      expressed in SOD-deficient E. coli and shown to be an active, Mn-type dismutase.
      This is the primary experimental evidence for the core function.
    action: ACCEPT
    reason: >-
      Gold-standard experimental support for the defining molecular function.
      Insensitivity to hydrogen peroxide and cyanide confirms the Mn-type (not Fe- or
      Cu/Zn-type) mechanism. Both worm MnSODs were expressed and assayed in this study.
      Core function.
    supported_by:
    - reference_id: PMID:9353332
      supporting_text: >-
        The expressed enzymes, which were not inhibited by hydrogen peroxide or
        cyanide, are dimeric, show quite different electrophoretic mobilities and
        isoelectric points, but exhibit comparable specific activities.
- term:
    id: GO:0019430
    label: removal of superoxide radicals
  evidence_type: IMP
  original_reference_id: PMID:9353332
  qualifier: involved_in
  review:
    summary: >-
      SOD-3 removes superoxide radicals: heterologous expression of the worm enzyme
      rescued SOD-deficient E. coli from methyl-viologen (paraquat) oxidative stress.
      This is the core biological process the enzyme serves.
    action: ACCEPT
    reason: >-
      Functionally correct core process. The evidence is heterologous complementation
      (protection of SOD-null E. coli against a superoxide generator) rather than a worm
      sod-3 loss-of-function phenotype, but it directly demonstrates superoxide-radical
      removal by the SOD-3 protein. Core process.
    supported_by:
    - reference_id: PMID:9353332
      supporting_text: >-
        Both proteins were shown to be active in E. coli, providing similar protection
        against methyl viologen-induced oxidative stress.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: IDA
  original_reference_id: PMID:17894411
  qualifier: located_in
  review:
    summary: >-
      Direct-assay (IDA) mitochondrial localization of SOD-3 (WormBase, from the full
      text of Wolf et al. 2008, the paper UniProt cites for the SUBCELLULAR LOCATION).
      Correct but generic relative to the mitochondrial matrix term.
    action: KEEP_AS_NON_CORE
    reason: >-
      Mitochondrial localization of this MnSOD is biologically unambiguous and
      concordant with the transit peptide and matrix localization; retained as a
      correct, less-specific companion to mitochondrial matrix (GO:0005759). The cached
      abstract of PMID:17894411 concerns JNK-1/DAF-16 signalling and does not itself
      state the mitochondrial localization (it is in the full text), so no
      sod-3-specific verbatim localization quote is available.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: ISS
  original_reference_id: PMID:9353332
  qualifier: located_in
  review:
    summary: >-
      Proposed more-specific localization: as a nuclear-encoded manganese superoxide
      dismutase bearing an N-terminal mitochondrial transit peptide, SOD-3 is imported
      into and acts within the mitochondrial matrix, the compartment where Fe/Mn-SOD
      family MnSODs reside. This refines the generic mitochondrion annotations.
    action: NEW
    reason: >-
      The existing localization annotations (IBA, SubCell IEA, IDA) all use the generic
      GO:0005739 mitochondrion. The transit peptide and Mn-SOD family assignment place
      SOD-3 specifically in the mitochondrial matrix, which is retained as the core
      location. Added as a NEW, more-specific companion inferred from sequence features
      (ISS) rather than by rewriting the trusted GOA ids.
    supported_by:
    - reference_id: PMID:9353332
      supporting_text: >-
        Both deduced protein sequences contain the expected N-terminal mitochondrial
        transit peptides.
core_functions:
- description: >-
    SOD-3 is a mitochondrial matrix manganese superoxide dismutase that catalyzes the
    dismutation of the superoxide anion radical to hydrogen peroxide and molecular
    oxygen (2 superoxide + 2 H+ -> H2O2 + O2; EC 1.15.1.1), a DAF-16/FOXO-inducible
    antioxidant defense of the mitochondrial matrix that complements the constitutive
    SOD-2.
  molecular_function:
    id: GO:0004784
    label: superoxide dismutase activity
  directly_involved_in:
  - id: GO:0019430
    label: removal of superoxide radicals
  locations:
  - id: GO:0005759
    label: mitochondrial matrix
  supported_by:
  - reference_id: PMID:9353332
    supporting_text: >-
      The expressed enzymes, which were not inhibited by hydrogen peroxide or cyanide,
      are dimeric, show quite different electrophoretic mobilities and isoelectric
      points, but exhibit comparable specific activities.
  - reference_id: PMID:9353332
    supporting_text: >-
      Both proteins were shown to be active in E. coli, providing similar protection
      against methyl viologen-induced oxidative stress.
- description: >-
    SOD-3 binds one catalytic manganese (Mn2+) ion per subunit, the redox-active
    cofactor required for the dismutase mechanism. Its Mn-type identity is established
    by insensitivity to hydrogen peroxide and cyanide, which inhibit Fe-type and
    Cu/Zn-type SODs respectively.
  molecular_function:
    id: GO:0030145
    label: manganese ion binding
  locations:
  - id: GO:0005759
    label: mitochondrial matrix
  supported_by:
  - reference_id: PMID:9353332
    supporting_text: >-
      The expressed enzymes, which were not inhibited by hydrogen peroxide or cyanide,
      are dimeric, show quite different electrophoretic mobilities and isoelectric
      points, but exhibit comparable specific activities.
proposed_new_terms: []
suggested_questions:
- question: >-
    Does the very low basal level of SOD-3 make a material contribution to superoxide
    scavenging in the wild-type mitochondrial matrix, or is SOD-3 essentially a
    stress- and DAF-16-inducible reserve isoform that matters mainly when SOD-2 is
    limiting?
- question: >-
    What is the mechanistic basis of the division of labour between the two nearly
    identical mitochondrial MnSODs, SOD-2 (constitutive, dominant) and SOD-3
    (DAF-16-inducible, low basal), given their distinct and sometimes opposite genetic
    interactions with electron-transport-chain mutants?
- question: >-
    Is the DAF-16-driven induction of sod-3 causally protective (extending lifespan or
    raising stress resistance), or is it primarily a transcriptional marker of DAF-16
    activity, given that eliminating both mitochondrial SODs does not suppress daf-2
    longevity?
suggested_experiments:
- description: >-
    Isoform-resolved, tagged-allele quantification and localization of SOD-3 versus
    SOD-2 across tissues, developmental stages and stress/DAF-16-active conditions, to
    define SOD-3's basal contribution and its supercomplex occupancy relative to SOD-2.
- description: >-
    Catalytically-dead (Mn-ligand mutant) versus wild-type sod-3 rescue in sod-3 and
    sod-2;sod-3 backgrounds, scoring supercomplex I:III:IV formation, complex I/II
    activity and ROS damage, to test whether SOD-3 acts by scavenging or as a
    catalysis-independent supercomplex stabilizer.
- description: >-
    Redox-biosensor (mitochondrial roGFP/HyPer) measurement of matrix superoxide/H2O2
    in wild type, sod-2, sod-3 and sod-2;sod-3 under DAF-16-activating conditions to
    resolve whether sod-3 induction lowers matrix superoxide and whether that change is
    required for the associated stress-resistance/longevity phenotypes.
knowledge_gaps:
- gap_statement: >-
    The functional division of labour between the two nearly identical mitochondrial
    manganese superoxide dismutases, SOD-3 and SOD-2, is undefined. It is unknown why
    C. elegans maintains a low-basal, DAF-16-inducible MnSOD (sod-3) alongside a
    constitutive, dominant one (sod-2), what distinguishes their substrates or
    sub-mitochondrial contexts, and why loss of sod-3 versus sod-2 produces different
    (sometimes opposite) genetic interactions with electron-transport-chain mutants.
  boundary: >-
    It is established that sod-2 and sod-3 are ~86% identical mitochondrial MnSODs, that
    sod-3 is normally expressed at very low levels and induced by DAF-16/insulin
    signalling whereas sod-2 is constitutive and dominant, that both localize to
    supercomplex I:III:IV, that loss of sod-3 (unlike sod-2) does not decrease complex I
    respiration and leaves blue-native supercomplex profiles normal, and that sod-3 has
    distinct genetic interactions with gas-1, mev-1 and isp-1. What is not established is
    the mechanistic basis of the non-redundancy at the level of substrate,
    sub-mitochondrial context, or partner; the authors of the key ETC study explicitly
    state that the sod-3/supercomplex interaction was still under investigation.
  gap_kind:
  - BIOLOGY
  dark_aspect: BP_DARK
  status: OPEN
  significance: >-
    Two paralogous mitochondrial MnSODs with divergent, non-redundant phenotypes are a
    clean model for how gene duplication partitions an antioxidant function, and the
    division of labour determines which isoform is limiting under which stress or
    signalling state.
  provenance:
  - reference_id: PMID:23895727
    supporting_text: >-
      However, the mutation sod-3 differed from sod-2 in its interactions with gas-1,
      mev-1 and isp-1.
  - reference_id: PMID:23895727
    supporting_text: >-
      Studies are now being undertaken to characterize the interaction of sod3 with
      supercomplex I:III:IV formation.
- gap_statement: >-
    Whether the DAF-16-driven induction of sod-3 is causally protective (increasing
    oxidative-stress resistance or extending lifespan) or is primarily a transcriptional
    readout of DAF-16 activity is unresolved. It is also unknown whether the very low
    basal SOD-3 level makes a material contribution to matrix superoxide scavenging in
    otherwise wild-type animals.
  boundary: >-
    It is established that sod-3 is a canonical DAF-16 target gene, expressed at very low
    basal levels and strongly induced upon DAF-16 nuclear translocation (including
    JNK-1-promoted translocation under thermal stress), and that its induction correlates
    with stress-resistant, long-lived states. However, simultaneous elimination of both
    mitochondrial SODs (sod-2 and sod-3) does not suppress the long lifespan of daf-2,
    arguing that sod-3 induction is not required for insulin/IGF-1-pathway longevity.
    What is not established is whether sod-3 induction confers a measurable protective
    benefit on its own, or whether it is chiefly a marker of the DAF-16 program.
  gap_kind:
  - BIOLOGY
  dark_aspect: BP_DARK
  status: OPEN
  significance: >-
    sod-3 is one of the most widely used transcriptional reporters of DAF-16/FOXO
    activity in aging and stress research; establishing whether its induction is
    protective or merely a marker directly affects how thousands of studies interpret
    sod-3 reporter readouts.
  provenance:
  - reference_id: PMID:23895727
    supporting_text: >-
      The activation of daf-16 increased expression of sod-3, an mtSOD normally
      expressed in very low levels in wild type worms
  - reference_id: PMID:23895727
    supporting_text: >-
      elimination of both mitochondrial sod-2 and sod-3 failed to suppress the long life
      span of daf-2
- gap_statement: >-
    Whether SOD-3's association with the respiratory supercomplex I:III:IV reflects only
    local superoxide scavenging at the site of ROS production, or whether SOD-3 can also
    act as a catalysis-independent structural stabilizer of the supercomplex (a role
    proposed for the mitochondrial SODs, and one SOD-3 may assume when SOD-2 is absent),
    is undetermined.
  boundary: >-
    It is established that SOD-3 co-localizes with the I:III:IV supercomplex by
    blue-native gel and that, unlike sod-2 loss, sod-3 loss does not by itself decrease
    complex I respiration or perturb the supercomplex profile. The open question is
    causality/mechanism: the mtSODs are proposed to stabilize the supercomplex, and the
    limited rise in supercomplex ROS damage in sod-2 animals suggests SOD-3 may perform
    this function when supercomplex levels fall, but a catalysis-independent structural
    role for SOD-3 remains unproven.
  gap_kind:
  - BIOLOGY
  dark_aspect: RESIDUAL_SUBGAP
  status: OPEN
  significance: >-
    Distinguishing a scavenging role from a structural role would determine whether SOD-3
    is a modular antioxidant or an integral stabilizer of the electron transport chain,
    with implications for how supercomplex integrity is maintained when the dominant
    SOD-2 is lost.
  provenance:
  - reference_id: PMID:23895727
    supporting_text: >-
      it is also possible that the mtSODs may directly serve as stabilizing factors in
      the I:III:IV supercomplex
  - reference_id: PMID:23895727
    supporting_text: >-
      the lack of a large increase in ROS damage to supercomplexes in a sod-2 animal may
      indicate that SOD-3 is also capable of performing this function, especially when
      the amount of supercomplex I:III:IV is reduced.