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this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.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.
The gene sod-2 (synonym: sdm-1; ORF name: F10D11.1) in Caenorhabditis elegans encodes Superoxide dismutase [Mn] 1, mitochondrial (EC 1.15.1.1), a member of the iron/manganese superoxide dismutase family. The gene is located on chromosome I and produces a precursor protein that is processed upon mitochondrial import (hunter1997cloningexpressionand pages 1-1). C. elegans possesses five superoxide dismutase genes: the cytoplasmic Cu/ZnSODs sod-1 and sod-5, the mitochondrial MnSODs sod-2 and sod-3, and the extracellular Cu/ZnSOD sod-4 (braeckman2016invivodetection pages 2-3). SOD-2 and SOD-3 are the products of a relatively recent gene duplication event, sharing 86.3% sequence identity (91.8% conservative identity), though their cDNAs are only 75.2% identical and the two proteins display distinct electrophoretic mobilities and isoelectric points (hunter1997cloningexpressionand pages 1-1, hunter1997cloningexpressionand pages 4-5).
The following table summarizes the key biochemical and functional properties of SOD-2:
| Property | SOD-2 summary | Evidence |
|---|---|---|
| Gene name | sod-2; historical synonym sdm-1 | (hunter1997cloningexpressionand pages 6-7, hunter1997cloningexpressionand pages 1-2) |
| Protein name | Manganese superoxide dismutase / mitochondrial superoxide dismutase (MnSOD) | (hunter1997cloningexpressionand pages 6-7, hunter1997cloningexpressionand pages 1-1) |
| UniProt accession | P31161 | (hunter1997cloningexpressionand pages 6-7) |
| Organism | Caenorhabditis elegans | (hunter1997cloningexpressionand pages 6-7, hunter1997cloningexpressionand pages 1-2) |
| Enzyme class | Superoxide dismutase, EC 1.15.1.1 | (hunter1997cloningexpressionand pages 1-1, hunter1997cloningexpressionand pages 1-2) |
| Catalytic reaction | Catalyzes dismutation of superoxide anion (O2•−) to hydrogen peroxide (H2O2) and oxygen (O2) | (hunter1997cloningexpressionand pages 1-1, sakamoto2017hydrogenperoxideproduced pages 1-2) |
| Physiologic substrate specificity | Primary substrate is superoxide radical generated in mitochondria; product H2O2 can serve signaling roles | (raamsdonk2009deletionofthe pages 2-3, sakamoto2017hydrogenperoxideproduced pages 10-11, branicky2022stimulationofrasdependent pages 2-3) |
| Metal cofactor | Manganese (Mn) | (hunter1997cloningexpressionand pages 6-7, hunter1997cloningexpressionand pages 1-1) |
| Molecular mass, monomer | 21,986 Da, 192 aa mature protein | (hunter1997cloningexpressionand pages 6-7, hunter1997cloningexpressionand pages 5-6) |
| Oligomeric state / dimer mass | Functions as an active dimer; measured mass 44,961 Da | (hunter1997cloningexpressionand pages 6-7, hunter1997cloningexpressionand pages 5-6) |
| Specific activity | 2516 units/mg protein when expressed in E. coli | (hunter1997cloningexpressionand pages 6-7) |
| Subcellular localization | Mitochondrial, specifically consistent with the mitochondrial matrix | (hunter1997cloningexpressionand pages 1-1, raamsdonk2009deletionofthe pages 2-3) |
| N-terminal transit peptide | Contains an N-terminal mitochondrial transit peptide; mature enzyme generated after targeting/processing | (hunter1997cloningexpressionand pages 1-1, hunter1997cloningexpressionand pages 4-5) |
| Physical mitochondrial association | Reported as physically associated with the I:III:IV respiratory supercomplex in the inner mitochondrial membrane context | (braeckman2016invivodetection pages 2-3) |
| Isoelectric point (pI) | 6.5 | (hunter1997cloningexpressionand pages 6-7) |
| Chromosome location | Chromosome I | (hunter1997cloningexpressionand pages 1-1) |
| Key domains / family | Member of the iron/manganese superoxide dismutase family; Mn/Fe SOD-type enzyme | (hunter1997cloningexpressionand pages 6-7, hunter1997cloningexpressionand pages 1-1) |
| Inhibitor sensitivity | Not inhibited by hydrogen peroxide or potassium cyanide, consistent with MnSOD rather than Cu/ZnSOD | (hunter1997cloningexpressionand pages 6-7, hunter1997cloningexpressionand pages 1-1) |
| Functional complementation | Expressed SOD-2 protects SOD-deficient E. coli from methyl viologen-induced oxidative stress | (hunter1997cloningexpressionand pages 1-1) |
| Core biological role in worm | Major mitochondrial superoxide detox enzyme; also shapes redox signaling by controlling conversion of mitochondrial superoxide into signaling-competent peroxide | (raamsdonk2009deletionofthe pages 2-3, branicky2022stimulationofrasdependent pages 2-3, onukwufor2022areversiblemitochondrial pages 8-9) |
| Lifespan phenotype of loss | Deletion of sod-2 extends lifespan in C. elegans despite increased oxidative stress sensitivity and oxidative damage | (raamsdonk2009deletionofthe pages 1-2, raamsdonk2009deletionofthe pages 6-8, raamsdonk2009deletionofthe pages 3-5) |
| Mitochondrial-function phenotype of loss | sod-2 mutants show decreased oxygen consumption, slow development, low brood size, and slow defecation, resembling long-lived mitochondrial mutants | (raamsdonk2009deletionofthe pages 1-2, raamsdonk2009deletionofthe pages 9-10, raamsdonk2009deletionofthe pages 5-6) |
| Interaction with mitochondrial mutants | Extends lifespan in clk-1, but shortens lifespan in isp-1 backgrounds; supports a mitochondrial threshold model | (raamsdonk2009deletionofthe pages 8-9, raamsdonk2009deletionofthe pages 10-11, raamsdonk2009deletionofthe pages 9-10) |
| Role in ROS signaling | Loss of SOD-2 elevates mitochondrial superoxide; longevity signaling requires downstream conversion involving SOD-1 and LET-60/RAS redox signaling | (branicky2022stimulationofrasdependent pages 2-3, raamsdonk2009deletionofthe pages 5-6) |
| Role in reproduction | SOD-2-generated H2O2 activates sperm pseudopod extension and is required for normal sperm activation | (sakamoto2017hydrogenperoxideproduced pages 10-11, sakamoto2017hydrogenperoxideproduced pages 1-2) |
| Comparison with SOD-3: localization/class | Both SOD-2 and SOD-3 are mitochondrial MnSODs with transit peptides and comparable specific activities | (hunter1997cloningexpressionand pages 1-1, hunter1997cloningexpressionand pages 4-5) |
| Comparison with SOD-3: biochemical differences | Both are dimers and active MnSODs, but show different electrophoretic mobilities and isoelectric points | (hunter1997cloningexpressionand pages 1-1) |
| Comparison with SOD-3: expression/regulation | sod-2 is relatively constitutive and similar in adult/dauer, whereas sod-3 is more dauer-associated and strongly induced in daf-2 mutants; sod-2 is more linked to SKN-1/p38 MAPK regulation, sod-3 to DAF-16/IIS | (honda1999thedaf‐2gene pages 6-7, yanase2020interactionbetweenthe pages 4-5, honda1999thedaf‐2gene pages 3-5) |
Table: This table summarizes the main biochemical, localization, and functional properties of C. elegans SOD-2, including direct comparisons with the paralog SOD-3. It is useful as a compact reference for annotation of sod-2/MnSOD in mitochondrial redox biology and lifespan signaling.
SOD-2 catalyzes the dismutation of the superoxide radical anion (O₂•⁻) into hydrogen peroxide (H₂O₂) and molecular oxygen (O₂), using a manganese cofactor at its active site (hunter1997cloningexpressionand pages 1-1, hunter1997cloningexpressionand pages 1-2). The reaction is:
2 O₂•⁻ + 2 H⁺ → H₂O₂ + O₂
Recombinant SOD-2 expressed in E. coli deficient in endogenous SODs exhibits a specific activity of 2,516 units/mg protein, comparable to that of its paralog SOD-3 (hunter1997cloningexpressionand pages 6-7). The mature SOD-2 monomer has a calculated molecular mass of 21,986 Da (192 amino acids) and functions as an active homodimer with a measured dimer mass of 44,961 Da (hunter1997cloningexpressionand pages 6-7, hunter1997cloningexpressionand pages 5-6). Consistent with its identity as an MnSOD, SOD-2 is not inhibited by hydrogen peroxide or potassium cyanide, distinguishing it biochemically from the Cu/Zn class of superoxide dismutases (hunter1997cloningexpressionand pages 6-7, hunter1997cloningexpressionand pages 1-1). Both recombinant SOD-2 and SOD-3 conferred comparable protection against methyl viologen (paraquat)-induced oxidative stress when expressed in SOD-deficient E. coli (hunter1997cloningexpressionand pages 1-1).
A critical insight from recent work is that the product of the SOD-2 catalyzed reaction—H₂O₂—is not merely a detoxified by-product but serves as a biologically active signaling molecule in multiple physiological contexts (sakamoto2017hydrogenperoxideproduced pages 10-11, branicky2022stimulationofrasdependent pages 2-3).
SOD-2 contains an N-terminal mitochondrial transit peptide that targets the protein to the mitochondrial matrix, where the transit peptide is cleaved to generate the mature enzyme (hunter1997cloningexpressionand pages 1-1, hunter1997cloningexpressionand pages 4-5). The positively charged residues in the transit peptide and at the beginning of the mature peptide are characteristic of mitochondrially targeted MnSODs across species (hunter1997cloningexpressionand pages 4-5). Within the mitochondria, SOD-2 has been reported to be physically associated with the I:III:IV respiratory supercomplex of the inner mitochondrial membrane (braeckman2016invivodetection pages 2-3), placing it in close proximity to the major sites of superoxide generation—particularly Complex I and Complex III of the electron transport chain (raamsdonk2009deletionofthe pages 2-3). This localization is functionally significant, as the mitochondrial matrix is the primary intracellular compartment where superoxide is actively produced during oxidative phosphorylation (raamsdonk2009deletionofthe pages 2-3, honda1999thedaf‐2gene pages 2-3).
SOD-2 is expressed under normal growth conditions in C. elegans, and its transcripts are trans-spliced to the SL-1 leader sequence, indicating mono-cistronic transcription (hunter1997cloningexpressionand pages 1-1, hunter1997cloningexpressionand pages 5-6). Northern blot analysis confirms a single transcript of approximately 800 nucleotides (hunter1997cloningexpressionand pages 5-6).
A key distinction between the two mitochondrial MnSODs involves their transcriptional regulation. sod-2 is expressed at relatively constitutive levels across developmental stages, including both adult and dauer stages, whereas sod-3 is more specifically induced during the dauer stage and in daf-2 (insulin receptor) mutants (honda1999thedaf‐2gene pages 6-7, honda1999thedaf‐2gene pages 3-5). Importantly, sod-2 mRNA levels in daf-2 mutants are comparable to wild-type, while sod-3 mRNA is markedly elevated (honda1999thedaf‐2gene pages 3-5). This indicates that sod-2 and sod-3 are regulated through distinct transcriptional programs: sod-2 is predominantly regulated by the SKN-1/Nrf2 transcription factor acting downstream of the p38 MAPK signaling pathway, whereas sod-3 is primarily a target of DAF-16/FOXO within the insulin/IGF-1 signaling (IIS) pathway (yanase2020interactionbetweenthe pages 4-5). Although putative DAF-16 binding elements (DBEs) exist in the sod-2 promoter, functional studies in daf-16 null mutants suggest these sites are non-functional for sod-2 regulation (yanase2020interactionbetweenthe pages 4-5).
One of the most striking and paradigm-challenging findings regarding sod-2 is that its deletion extends lifespan in C. elegans, in stark contrast to yeast, flies, and mice where SOD2 loss shortens lifespan (raamsdonk2009deletionofthe pages 1-2, raamsdonk2009deletionofthe pages 2-3). Van Raamsdonk and Hekimi (2009) demonstrated that sod-2 deletion mutants live significantly longer than wild-type worms, despite exhibiting increased oxidative damage (measured as oxidatively modified proteins) and increased sensitivity to paraquat- and juglone-induced oxidative stress (raamsdonk2009deletionofthe pages 1-2, raamsdonk2009deletionofthe pages 3-5). This paradox fundamentally challenged the oxidative stress theory of aging.
The mechanism underlying this lifespan extension appears to involve altered mitochondrial function rather than changes in oxidative stress per se. sod-2 mutant worms display a suite of phenotypes characteristic of long-lived mitochondrial mutants: slow post-embryonic development, reduced brood size, slow defecation cycle rate, and critically, decreased whole-worm oxygen consumption (raamsdonk2009deletionofthe pages 1-2, raamsdonk2009deletionofthe pages 5-6, raamsdonk2009deletionofthe pages 6-8). Genetic interaction studies revealed that sod-2 deletion markedly extends lifespan (by ~15 days) in clk-1 mutant backgrounds (which have mildly impaired mitochondrial function), but decreases lifespan (by ~25 days) in isp-1 mutant backgrounds (which already have >50% reduced respiration) (raamsdonk2009deletionofthe pages 8-9, raamsdonk2009deletionofthe pages 9-10, raamsdonk2009deletionofthe pages 6-8). This led to a mitochondrial threshold model: moderate reductions in mitochondrial function can activate compensatory longevity-promoting programs, but when dysfunction exceeds a critical threshold, the organism can no longer compensate and lifespan shortens (raamsdonk2009deletionofthe pages 10-11, raamsdonk2009deletionofthe pages 9-10).
Recent work by Branicky et al. (2022) has elucidated a mechanistic pathway explaining how loss of SOD-2 extends lifespan through a RAS-dependent ROS signaling (RDRS) pathway. Loss of SOD-2 elevates mitochondrial superoxide levels. This superoxide exits the mitochondria and is converted to hydrogen peroxide by cytoplasmic SOD-1 (Cu/ZnSOD). The H₂O₂ then acts on a redox-sensitive cysteine residue (C118) of LET-60/RAS, modulating its activity and triggering a global program of gene expression that affects approximately half of the genome (branicky2022stimulationofrasdependent pages 2-3). Critically, the longevity benefit of sod-2 loss requires SOD-1: when SOD-1 is also deleted, the lifespan extension of sod-2 mutants is completely suppressed, demonstrating that the longevity signal is not from superoxide itself but from the SOD-1-generated H₂O₂ acting through cytoplasmic RAS signaling (branicky2022stimulationofrasdependent pages 2-3).
Onukwufor et al. (2022) demonstrated that SOD-2 is required for Complex I-derived ROS to drive behavioral responses in C. elegans. Using optogenetic tools to generate site-specific mitochondrial ROS, they showed that SOD-2/SOD-3-dependent conversion of superoxide to H₂O₂ is necessary for ROS-induced locomotory remodeling, specifically hypoxic avoidance behavior. In the absence of SOD-2, the behavioral response to Complex I ROS is abolished, though it can be rescued by a SOD mimetic compound (MnPyP) (onukwufor2022areversiblemitochondrial pages 8-9, onukwufor2022areversiblemitochondrial pages 6-8). This establishes SOD-2 as a critical mediator linking mitochondrial ROS production to acute behavioral outputs.
Senchuk et al. (2018) showed that elevated ROS in sod-2 mutants contributes to DAF-16/FOXO activation, which is required for the full longevity of long-lived mitochondrial mutants. The transcriptional changes in mitochondrial mutants overlap significantly with those in long-lived daf-2 (insulin/IGF-1 receptor) mutants, and DAF-16 along with multiple DAF-16-interacting proteins are required for full lifespan extension (prasad2013evaluationofrole pages 3-4). Overexpression of SOD-2 has also been shown to extend lifespan in a daf-16-dependent manner, indicating that both gain and loss of SOD-2 function can modulate longevity signaling through DAF-16, albeit through distinct mechanisms (prasad2013evaluationofrole pages 3-4).
Sakamoto and Imai (2017) discovered a surprising role for SOD-2 in sperm activation in C. elegans. The H₂O₂ produced by SOD-2's catalytic activity acts as a positive signaling molecule required for pseudopod extension during sperm activation. In sod-1;sod-2 double mutant sperm, pseudopod extension is defective, leading to significantly reduced brood size (sakamoto2017hydrogenperoxideproduced pages 10-11, sakamoto2017hydrogenperoxideproduced pages 1-2). Exogenous application of H₂O₂ rescues the activation defects of double mutant sperm, while the H₂O₂ scavenger ebselen completely inhibits pseudopod extension in wild-type sperm (sakamoto2017hydrogenperoxideproduced pages 10-11). Analysis of single mutants demonstrated that sod-2, rather than sod-1, is the specific SOD gene required for proper pseudopod extension during sperm activation (sakamoto2017hydrogenperoxideproduced pages 10-11, sakamoto2017hydrogenperoxideproduced pages 1-2).
SOD-2 plays a critical protective role in contexts of compromised mitochondrial morphology. Kanazawa et al. (2008) demonstrated that eat-3 mutants (defective in mitochondrial inner membrane fusion, homologous to human OPA1) are highly sensitive to loss of sod-2. The eat-3 mutants upregulate SOD-2 protein levels more than two-fold as a compensatory response, and depletion of sod-2 by RNAi or genetic mutation causes a strong negative effect on survival and growth in the eat-3 background (kanazawa2008thec.elegans pages 8-9, kanazawa2008thec.elegans pages 1-2). This effect is specific to sod-2, as loss of other SOD genes (sod-1, sod-3, sod-5) has only modest effects in eat-3 animals (kanazawa2008thec.elegans pages 9-10). The selective dependency on SOD-2 is consistent with its mitochondrial matrix localization, where disrupted cristae morphology in eat-3 mutants leads to increased free radical production that must be managed locally (kanazawa2008thec.elegans pages 9-10).
The following table summarizes the key pathways in which SOD-2 participates:
| Pathway | Key components | Role of SOD-2 | Biological outcome | Evidence |
|---|---|---|---|---|
| Mitochondrial superoxide detoxification | Mitochondrial electron transport chain; superoxide (O2•−); Mn cofactor; SOD-2 in mitochondrial matrix; H2O2/O2 products | Primary mitochondrial Mn-superoxide dismutase that converts superoxide to hydrogen peroxide and oxygen; active dimeric enzyme with mitochondrial transit peptide and matrix localization | Limits mitochondrial superoxide burden and contributes to basal antioxidant defense; loss increases oxidative stress sensitivity and oxidative damage even when lifespan is not shortened | (hunter1997cloningexpressionand pages 6-7, hunter1997cloningexpressionand pages 1-1, raamsdonk2009deletionofthe pages 2-3, raamsdonk2009deletionofthe pages 3-5) |
| RAS-dependent ROS signaling (RDRS) | Mitochondrial superoxide; SOD-2; cytosolic SOD-1; H2O2; LET-60/RAS C118 redox switch | Loss of SOD-2 raises mitochondrial superoxide; longevity signal requires downstream conversion by SOD-1 to H2O2, which oxidizes LET-60/RAS and activates RDRS | Global transcriptional remodeling and lifespan extension from mitochondrial ROS signaling rather than simple detoxification | (branicky2022stimulationofrasdependent pages 2-3, raamsdonk2009deletionofthe pages 5-6) |
| p38 MAPK/SKN-1/Nrf2 regulation of sod-2 | p38 MAPK pathway; SKN-1/Nrf2; sod-2 promoter | sod-2 is regulated predominantly by SKN-1 rather than DAF-16 under stress-responsive conditions, especially in molecular compensation among sod mutants | Supports stress adaptation and longevity-associated redox homeostasis under intracellular oxidative stress | (yanase2020interactionbetweenthe pages 4-5) |
| Insulin/IGF-1 signaling (IIS) via DAF-2/DAF-16 | DAF-2 insulin/IGF-1 receptor; DAF-16/FoxO; MnSOD genes sod-2 and sod-3 | sod-2 is part of the MnSOD antioxidant network linked to longevity signaling, but unlike sod-3 it is not strongly induced in daf-2 mutants and appears less directly controlled by DAF-16 | Contributes to oxidative stress resistance framework of IIS, while sod-3 is the more prominent dauer/DAF-16-responsive MnSOD output | (honda1999thedaf‐2gene pages 2-3, honda1999thedaf‐2gene pages 6-7, honda1999thedaf‐2gene pages 3-5) |
| Mitochondrial unfolded protein response (UPRmt) / mitochondrial dysfunction programs | Mitochondrial stress; mitochondrial proteostasis pathways; respiratory dysfunction; stress-response genes including SOD enzymes | SOD-2 is repeatedly discussed as part of mitochondrial stress-response programs and as a mitochondrial redox effector whose loss phenocopies long-lived mitochondrial mutants with reduced respiration | Links mitochondrial dysfunction to compensatory stress programs and altered lifespan trajectories | (raamsdonk2009deletionofthe pages 1-2, raamsdonk2009deletionofthe pages 5-6) |
| Complex I ROS signaling and hypoxic avoidance behavior | Complex I-derived ROS; SOD-2/SOD-3; H2O2; redox-sensitive thiol switch on NDUF-2.1-related pathway; locomotory/hypoxia avoidance circuitry | SOD-2 is required to convert complex I-derived superoxide into H2O2 that mediates behavioral signaling; loss of sod-2 abolishes ROS-triggered avoidance/photolocomotory responses | Enables mitochondrial ROS to function as a signal for hypoxic avoidance and acute behavioral adaptation | (onukwufor2022areversiblemitochondrial pages 8-9, onukwufor2022areversiblemitochondrial pages 6-8) |
| Sperm activation via H2O2 signaling | SOD-2; SOD-1; H2O2; Pronase-responsive sperm activation; pseudopod extension machinery | SOD-2-generated H2O2 acts as a positive signaling molecule required for sperm activation and pseudopod extension; exogenous H2O2 rescues activation defects in sod-1;sod-2 mutants | Promotes normal sperm motility/activation and supports fertility/brood size | (sakamoto2017hydrogenperoxideproduced pages 10-11, sakamoto2017hydrogenperoxideproduced pages 1-2, sakamoto2017hydrogenperoxideproduced pages 8-10) |
Table: This table summarizes the main signaling and biochemical pathways involving C. elegans SOD-2, emphasizing where it acts as a detoxifying enzyme versus a redox-signaling mediator. It is useful for functional annotation because it connects SOD-2 to localization, pathway context, and experimentally observed organismal outcomes.
C. elegans SOD-2 is a mitochondrial matrix-localized manganese superoxide dismutase that catalyzes the dismutation of superoxide radicals to hydrogen peroxide and oxygen. Beyond its canonical antioxidant function, SOD-2 has emerged as a critical node in mitochondrial redox signaling. Its enzymatic product, H₂O₂, serves as a signaling molecule in at least three distinct biological contexts: (1) RAS-dependent longevity signaling, where mitochondrial superoxide escaping from the matrix is converted to cytoplasmic H₂O₂ by SOD-1 to activate LET-60/RAS (branicky2022stimulationofrasdependent pages 2-3); (2) sperm activation, where SOD-2-derived H₂O₂ directly drives pseudopod extension (sakamoto2017hydrogenperoxideproduced pages 10-11, sakamoto2017hydrogenperoxideproduced pages 1-2); and (3) behavioral responses, where SOD-2-dependent H₂O₂ production mediates Complex I ROS-triggered locomotory adaptation (onukwufor2022areversiblemitochondrial pages 8-9, onukwufor2022areversiblemitochondrial pages 6-8). The paradoxical lifespan extension upon sod-2 deletion reflects altered mitochondrial function and activation of compensatory longevity programs, rather than a simple reduction in oxidative damage (raamsdonk2009deletionofthe pages 1-2, raamsdonk2009deletionofthe pages 5-6). Transcriptionally, sod-2 is regulated predominantly by the SKN-1/Nrf2 pathway through p38 MAPK signaling, distinguishing it from its paralog sod-3, which is a primary target of DAF-16/FOXO in the insulin/IGF-1 signaling pathway (yanase2020interactionbetweenthe pages 4-5). Together, these findings position SOD-2 as both a protective antioxidant enzyme and a redox-signaling mediator at the interface of mitochondrial function, aging, reproduction, and behavior.
References
(hunter1997cloningexpressionand pages 1-1): Thérèse Hunter, William H. Bannister, and Gary J. Hunter. Cloning, expression, and characterization of two manganese superoxide dismutases from caenorhabditis elegans *. The Journal of Biological Chemistry, 272:28652-28659, Nov 1997. URL: https://doi.org/10.1074/jbc.272.45.28652, doi:10.1074/jbc.272.45.28652. This article has 183 citations.
(braeckman2016invivodetection pages 2-3): Bart P. Braeckman, Arne Smolders, Patricia Back, and Sasha De Henau. In vivo detection of reactive oxygen species and redox status in caenorhabditis elegans. Antioxidants & redox signaling, 25 10:577-92, Oct 2016. URL: https://doi.org/10.1089/ars.2016.6751, doi:10.1089/ars.2016.6751. This article has 64 citations and is from a domain leading peer-reviewed journal.
(hunter1997cloningexpressionand pages 4-5): Thérèse Hunter, William H. Bannister, and Gary J. Hunter. Cloning, expression, and characterization of two manganese superoxide dismutases from caenorhabditis elegans *. The Journal of Biological Chemistry, 272:28652-28659, Nov 1997. URL: https://doi.org/10.1074/jbc.272.45.28652, doi:10.1074/jbc.272.45.28652. This article has 183 citations.
(hunter1997cloningexpressionand pages 6-7): Thérèse Hunter, William H. Bannister, and Gary J. Hunter. Cloning, expression, and characterization of two manganese superoxide dismutases from caenorhabditis elegans *. The Journal of Biological Chemistry, 272:28652-28659, Nov 1997. URL: https://doi.org/10.1074/jbc.272.45.28652, doi:10.1074/jbc.272.45.28652. This article has 183 citations.
(hunter1997cloningexpressionand pages 1-2): Thérèse Hunter, William H. Bannister, and Gary J. Hunter. Cloning, expression, and characterization of two manganese superoxide dismutases from caenorhabditis elegans *. The Journal of Biological Chemistry, 272:28652-28659, Nov 1997. URL: https://doi.org/10.1074/jbc.272.45.28652, doi:10.1074/jbc.272.45.28652. This article has 183 citations.
(sakamoto2017hydrogenperoxideproduced pages 1-2): Taro Sakamoto and Hirotaka Imai. Hydrogen peroxide produced by superoxide dismutase sod-2 activates sperm in caenorhabditis elegans. Journal of Biological Chemistry, 292:14804-14813, Sep 2017. URL: https://doi.org/10.1074/jbc.m117.788901, doi:10.1074/jbc.m117.788901. This article has 105 citations and is from a domain leading peer-reviewed journal.
(raamsdonk2009deletionofthe pages 2-3): Jeremy M. Van Raamsdonk and Siegfried Hekimi. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in caenorhabditis elegans. PLoS Genetics, 5:e1000361, Feb 2009. URL: https://doi.org/10.1371/journal.pgen.1000361, doi:10.1371/journal.pgen.1000361. This article has 699 citations and is from a domain leading peer-reviewed journal.
(sakamoto2017hydrogenperoxideproduced pages 10-11): Taro Sakamoto and Hirotaka Imai. Hydrogen peroxide produced by superoxide dismutase sod-2 activates sperm in caenorhabditis elegans. Journal of Biological Chemistry, 292:14804-14813, Sep 2017. URL: https://doi.org/10.1074/jbc.m117.788901, doi:10.1074/jbc.m117.788901. This article has 105 citations and is from a domain leading peer-reviewed journal.
(branicky2022stimulationofrasdependent pages 2-3): Robyn Branicky, Ying Wang, Arman Khaki, Ju-Ling Liu, Maximilian Kramer-Drauberg, and Siegfried Hekimi. Stimulation of ras-dependent ros signaling extends longevity by modulating a developmental program of global gene expression. Dec 2022. URL: https://doi.org/10.1126/sciadv.adc9851, doi:10.1126/sciadv.adc9851. This article has 17 citations and is from a highest quality peer-reviewed journal.
(hunter1997cloningexpressionand pages 5-6): Thérèse Hunter, William H. Bannister, and Gary J. Hunter. Cloning, expression, and characterization of two manganese superoxide dismutases from caenorhabditis elegans *. The Journal of Biological Chemistry, 272:28652-28659, Nov 1997. URL: https://doi.org/10.1074/jbc.272.45.28652, doi:10.1074/jbc.272.45.28652. This article has 183 citations.
(onukwufor2022areversiblemitochondrial pages 8-9): John O. Onukwufor, M. Arsalan Farooqi, Anežka Vodičková, Shon A. Koren, Aksana Baldzizhar, Brandon J. Berry, Gisela Beutner, George A. Porter, Vsevolod Belousov, Alan Grossfield, and Andrew P. Wojtovich. A reversible mitochondrial complex i thiol switch mediates hypoxic avoidance behavior in c. elegans. Nature Communications, May 2022. URL: https://doi.org/10.1038/s41467-022-30169-y, doi:10.1038/s41467-022-30169-y. This article has 44 citations and is from a highest quality peer-reviewed journal.
(raamsdonk2009deletionofthe pages 1-2): Jeremy M. Van Raamsdonk and Siegfried Hekimi. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in caenorhabditis elegans. PLoS Genetics, 5:e1000361, Feb 2009. URL: https://doi.org/10.1371/journal.pgen.1000361, doi:10.1371/journal.pgen.1000361. This article has 699 citations and is from a domain leading peer-reviewed journal.
(raamsdonk2009deletionofthe pages 6-8): Jeremy M. Van Raamsdonk and Siegfried Hekimi. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in caenorhabditis elegans. PLoS Genetics, 5:e1000361, Feb 2009. URL: https://doi.org/10.1371/journal.pgen.1000361, doi:10.1371/journal.pgen.1000361. This article has 699 citations and is from a domain leading peer-reviewed journal.
(raamsdonk2009deletionofthe pages 3-5): Jeremy M. Van Raamsdonk and Siegfried Hekimi. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in caenorhabditis elegans. PLoS Genetics, 5:e1000361, Feb 2009. URL: https://doi.org/10.1371/journal.pgen.1000361, doi:10.1371/journal.pgen.1000361. This article has 699 citations and is from a domain leading peer-reviewed journal.
(raamsdonk2009deletionofthe pages 9-10): Jeremy M. Van Raamsdonk and Siegfried Hekimi. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in caenorhabditis elegans. PLoS Genetics, 5:e1000361, Feb 2009. URL: https://doi.org/10.1371/journal.pgen.1000361, doi:10.1371/journal.pgen.1000361. This article has 699 citations and is from a domain leading peer-reviewed journal.
(raamsdonk2009deletionofthe pages 5-6): Jeremy M. Van Raamsdonk and Siegfried Hekimi. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in caenorhabditis elegans. PLoS Genetics, 5:e1000361, Feb 2009. URL: https://doi.org/10.1371/journal.pgen.1000361, doi:10.1371/journal.pgen.1000361. This article has 699 citations and is from a domain leading peer-reviewed journal.
(raamsdonk2009deletionofthe pages 8-9): Jeremy M. Van Raamsdonk and Siegfried Hekimi. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in caenorhabditis elegans. PLoS Genetics, 5:e1000361, Feb 2009. URL: https://doi.org/10.1371/journal.pgen.1000361, doi:10.1371/journal.pgen.1000361. This article has 699 citations and is from a domain leading peer-reviewed journal.
(raamsdonk2009deletionofthe pages 10-11): Jeremy M. Van Raamsdonk and Siegfried Hekimi. Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in caenorhabditis elegans. PLoS Genetics, 5:e1000361, Feb 2009. URL: https://doi.org/10.1371/journal.pgen.1000361, doi:10.1371/journal.pgen.1000361. This article has 699 citations and is from a domain leading peer-reviewed journal.
(honda1999thedaf‐2gene pages 6-7): Yoko Honda and Shuji Honda. The daf‐2 gene network for longevity regulates oxidative stress resistance and mn‐superoxide dismutase gene expression in caenorhabditis elegans. The FASEB Journal, 13:1385-1393, Aug 1999. URL: https://doi.org/10.1096/fasebj.13.11.1385, doi:10.1096/fasebj.13.11.1385. This article has 968 citations.
(yanase2020interactionbetweenthe pages 4-5): Sumino Yanase, Kayo Yasuda, and Naoaki Ishii. Interaction between the ins/igf-1 and p38 mapk signaling pathways in molecular compensation of sod genes and modulation related to intracellular ros levels in c. elegans. Sep 2020. URL: https://doi.org/10.1016/j.bbrep.2020.100796, doi:10.1016/j.bbrep.2020.100796. This article has 37 citations and is from a peer-reviewed journal.
(honda1999thedaf‐2gene pages 3-5): Yoko Honda and Shuji Honda. The daf‐2 gene network for longevity regulates oxidative stress resistance and mn‐superoxide dismutase gene expression in caenorhabditis elegans. The FASEB Journal, 13:1385-1393, Aug 1999. URL: https://doi.org/10.1096/fasebj.13.11.1385, doi:10.1096/fasebj.13.11.1385. This article has 968 citations.
(honda1999thedaf‐2gene pages 2-3): Yoko Honda and Shuji Honda. The daf‐2 gene network for longevity regulates oxidative stress resistance and mn‐superoxide dismutase gene expression in caenorhabditis elegans. The FASEB Journal, 13:1385-1393, Aug 1999. URL: https://doi.org/10.1096/fasebj.13.11.1385, doi:10.1096/fasebj.13.11.1385. This article has 968 citations.
(onukwufor2022areversiblemitochondrial pages 6-8): John O. Onukwufor, M. Arsalan Farooqi, Anežka Vodičková, Shon A. Koren, Aksana Baldzizhar, Brandon J. Berry, Gisela Beutner, George A. Porter, Vsevolod Belousov, Alan Grossfield, and Andrew P. Wojtovich. A reversible mitochondrial complex i thiol switch mediates hypoxic avoidance behavior in c. elegans. Nature Communications, May 2022. URL: https://doi.org/10.1038/s41467-022-30169-y, doi:10.1038/s41467-022-30169-y. This article has 44 citations and is from a highest quality peer-reviewed journal.
(prasad2013evaluationofrole pages 3-4): Kedar Prasad and Stephen Bondy. Evaluation of role of oxidative stress on aging in caenorhabditis elegans: a brief review. Current Aging Science, 6:215-219, Dec 2013. URL: https://doi.org/10.2174/18746098112059990031, doi:10.2174/18746098112059990031. This article has 13 citations.
(kanazawa2008thec.elegans pages 8-9): Takayuki Kanazawa, Mauro Zappaterra, Ayako Hasegawa, Ashley P Wright, Erin D Newman-Smith, Karolyn F Buttle, Kent L McDonald, Carmen Mannella, and Alex van der Bliek. The c. elegans opa1 homologue eat-3 is essential for resistance to free radicals. PLoS Genetics, 4:e39, Feb 2008. URL: https://doi.org/10.1371/journal.pgen.1000022, doi:10.1371/journal.pgen.1000022. This article has 198 citations and is from a domain leading peer-reviewed journal.
(kanazawa2008thec.elegans pages 1-2): Takayuki Kanazawa, Mauro Zappaterra, Ayako Hasegawa, Ashley P Wright, Erin D Newman-Smith, Karolyn F Buttle, Kent L McDonald, Carmen Mannella, and Alex van der Bliek. The c. elegans opa1 homologue eat-3 is essential for resistance to free radicals. PLoS Genetics, 4:e39, Feb 2008. URL: https://doi.org/10.1371/journal.pgen.1000022, doi:10.1371/journal.pgen.1000022. This article has 198 citations and is from a domain leading peer-reviewed journal.
(kanazawa2008thec.elegans pages 9-10): Takayuki Kanazawa, Mauro Zappaterra, Ayako Hasegawa, Ashley P Wright, Erin D Newman-Smith, Karolyn F Buttle, Kent L McDonald, Carmen Mannella, and Alex van der Bliek. The c. elegans opa1 homologue eat-3 is essential for resistance to free radicals. PLoS Genetics, 4:e39, Feb 2008. URL: https://doi.org/10.1371/journal.pgen.1000022, doi:10.1371/journal.pgen.1000022. This article has 198 citations and is from a domain leading peer-reviewed journal.
(sakamoto2017hydrogenperoxideproduced pages 8-10): Taro Sakamoto and Hirotaka Imai. Hydrogen peroxide produced by superoxide dismutase sod-2 activates sperm in caenorhabditis elegans. Journal of Biological Chemistry, 292:14804-14813, Sep 2017. URL: https://doi.org/10.1074/jbc.m117.788901, doi:10.1074/jbc.m117.788901. This article has 105 citations and is from a domain leading peer-reviewed journal.