SdhB
D. melanogaster
Succinate dehydrogenase, subunit B (iron-sulfur)
What the model saw
Gene: SdhB Organism: Drosophila melanogaster Known functions: Succinate dehydrogenase, subunit B (iron-sulfur). succinate dehydrogenase, subunit B (iron-sulfur). 2 iron, 2 sulfur cluster binding. 3 iron, 4 sulfur cluster binding. 4 iron, 4 sulfur cluster binding. electron transfer activity. iron-sulfur cluster binding. oxidoreductase activity. succinate dehydrogenase (quinone) activity. ubiquinone binding.
View unredacted entry
Succinate dehydrogenase, subunit B (iron-sulfur). succinate dehydrogenase, subunit B (iron-sulfur). 2 iron, 2 sulfur cluster binding. 3 iron, 4 sulfur cluster binding. 4 iron, 4 sulfur cluster binding. electron transfer activity. iron-sulfur cluster binding. oxidoreductase activity. succinate dehydrogenase (quinone) activity. ubiquinone binding.
Solver output
SdhB encodes the iron-sulfur subunit of succinate dehydrogenase (Complex II of the mitochondrial electron transport chain), which catalyzes the oxidation of succinate to fumarate while transferring electrons to ubiquinone. This reaction is central to both the TCA cycle and oxidative phosphorylation. Loss of SdhB function impairs Complex II electron transfer, leading to succinate accumulation, reduced mitochondrial membrane potential, increased reactive oxygen species (ROS) production via electron leak, and diminished ATP synthesis — all hallmarks of mitochondrial dysfunction associated with accelerated aging. Proper Complex II activity also suppresses succinate-driven HIF-1α stabilization and pseudohypoxic signaling, which can promote cellular senescence and metabolic dysregulation. In Drosophila, RNAi knockdown of SdhB has been shown to shorten lifespan and impair mitochondrial function, consistent with a pro-longevity role for the wild-type gene.
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 SdhB in Drosophila melanogaster. The mechanistic reasoning is thorough and accurate: SdhB encodes the iron-sulfur subunit of Complex II (succinate dehydrogenase), and loss of function leads to mitochondrial dysfunction, ROS production, and shortened lifespan. The model correctly identifies that wild-type SdhB supports longevity, and references RNAi knockdown studies in Drosophila that shorten lifespan. The additional mention of HIF-1α/pseudohypoxic signaling via succinate accumulation is a valid and sophisticated mechanistic point. Confidence of 0.72 is appropriate given the specificity of the claim.
Raw API responses
solver
{
"reasoning": "SdhB encodes the iron-sulfur subunit of succinate dehydrogenase (Complex II of the mitochondrial electron transport chain), which catalyzes the oxidation of succinate to fumarate while transferring electrons to ubiquinone. This reaction is central to both the TCA cycle and oxidative phosphorylation. Loss of SdhB function impairs Complex II electron transfer, leading to succinate accumulation, reduced mitochondrial membrane potential, increased reactive oxygen species (ROS) production via electron leak, and diminished ATP synthesis — all hallmarks of mitochondrial dysfunction associated with accelerated aging. Proper Complex II activity also suppresses succinate-driven HIF-1α stabilization and pseudohypoxic signaling, which can promote cellular senescence and metabolic dysregulation. In Drosophila, RNAi knockdown of SdhB has been shown to shorten lifespan and impair mitochondrial function, consistent with a pro-longevity role for the wild-type gene.",
"confidence": 0.72,
"key_pathways": [
"mitochondrial electron transport chain (Complex II)",
"TCA cycle / succinate oxidation",
"ubiquinone (CoQ) redox cycling"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for SdhB in Drosophila melanogaster. The mechanistic reasoning is thorough and accurate: SdhB encodes the iron-sulfur subunit of Complex II (succinate dehydrogenase), and loss of function leads to mitochondrial dysfunction, ROS production, and shortened lifespan. The model correctly identifies that wild-type SdhB supports longevity, and references RNAi knockdown studies in Drosophila that shorten lifespan. The additional mention of HIF-1α/pseudohypoxic signaling via succinate accumulation is a valid and sophisticated mechanistic point. Confidence of 0.72 is appropriate given the specificity of the claim.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}