SdhC
D. melanogaster
Succinate dehydrogenase, subunit C
What the model saw
Gene: SdhC Organism: Drosophila melanogaster Known functions: Succinate dehydrogenase, subunit C. succinate dehydrogenase, subunit C. electron transfer activity. protein-membrane adaptor activity. succinate dehydrogenase (quinone) activity.
View unredacted entry
Succinate dehydrogenase, subunit C. succinate dehydrogenase, subunit C. electron transfer activity. protein-membrane adaptor activity. succinate dehydrogenase (quinone) activity.
Solver output
SdhC encodes the membrane-anchoring subunit C of succinate dehydrogenase (Complex II), which couples the oxidation of succinate to fumarate in the TCA cycle with electron transfer to ubiquinone in the mitochondrial electron transport chain. Proper Complex II function is essential for efficient oxidative phosphorylation and limiting electron leak that generates reactive oxygen species (ROS). Loss or impairment of SdhC disrupts electron transfer activity and succinate dehydrogenase (quinone) activity, leading to succinate accumulation, increased mitochondrial ROS production, and impaired ATP synthesis — all hallmarks of mitochondrial dysfunction associated with accelerated aging. Its protein-membrane adaptor activity is critical for anchoring the catalytic subunits (SdhA/SdhB) to the inner mitochondrial membrane, making it structurally indispensable for Complex II integrity. In Drosophila, mitochondrial electron transport chain integrity is a well-established determinant of lifespan, and functional Complex II suppresses oxidative damage that drives aging.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model correctly predicted pro_longevity for SdhC in Drosophila melanogaster. The mechanistic reasoning is sound and well-grounded: SdhC is the membrane-anchoring subunit of Complex II (succinate dehydrogenase), and its proper function is essential for mitochondrial electron transport chain integrity, limiting ROS production, and maintaining efficient oxidative phosphorylation. The model correctly identifies that loss of SdhC would lead to mitochondrial dysfunction and accelerated aging, making it pro-longevity when functional. The reasoning about succinate accumulation, ROS production, and ATP synthesis impairment upon SdhC loss is biochemically accurate. The confidence of 0.72 is appropriate given the indirect nature of the inference (the model is reasoning from known biochemistry rather than citing specific Drosophila lifespan experiments). The reasoning is slightly generic in that it doesn't cite specific experimental evidence from Drosophila studies on SdhC, but the overall logic is correct and well-articulated.
Raw API responses
solver
{
"reasoning": "SdhC encodes the membrane-anchoring subunit C of succinate dehydrogenase (Complex II), which couples the oxidation of succinate to fumarate in the TCA cycle with electron transfer to ubiquinone in the mitochondrial electron transport chain. Proper Complex II function is essential for efficient oxidative phosphorylation and limiting electron leak that generates reactive oxygen species (ROS). Loss or impairment of SdhC disrupts electron transfer activity and succinate dehydrogenase (quinone) activity, leading to succinate accumulation, increased mitochondrial ROS production, and impaired ATP synthesis — all hallmarks of mitochondrial dysfunction associated with accelerated aging. Its protein-membrane adaptor activity is critical for anchoring the catalytic subunits (SdhA/SdhB) to the inner mitochondrial membrane, making it structurally indispensable for Complex II integrity. In Drosophila, mitochondrial electron transport chain integrity is a well-established determinant of lifespan, and functional Complex II suppresses oxidative damage that drives aging.",
"confidence": 0.72,
"key_pathways": [
"mitochondrial electron transport chain (Complex II)",
"TCA cycle / succinate-fumarate oxidation",
"reactive oxygen species (ROS) homeostasis"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for SdhC in Drosophila melanogaster. The mechanistic reasoning is sound and well-grounded: SdhC is the membrane-anchoring subunit of Complex II (succinate dehydrogenase), and its proper function is essential for mitochondrial electron transport chain integrity, limiting ROS production, and maintaining efficient oxidative phosphorylation. The model correctly identifies that loss of SdhC would lead to mitochondrial dysfunction and accelerated aging, making it pro-longevity when functional. The reasoning about succinate accumulation, ROS production, and ATP synthesis impairment upon SdhC loss is biochemically accurate. The confidence of 0.72 is appropriate given the indirect nature of the inference (the model is reasoning from known biochemistry rather than citing specific Drosophila lifespan experiments). The reasoning is slightly generic in that it doesn't cite specific experimental evidence from Drosophila studies on SdhC, but the overall logic is correct and well-articulated.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}