atp-3
C. elegans
Oligomycin sensitivity conferral protein
What the model saw
Gene: atp-3 Organism: Caenorhabditis elegans Known functions: Oligomycin sensitivity conferral protein. proton-transporting ATP synthase activity, rotational mechanism.
View unredacted entry
Oligomycin sensitivity conferral protein. proton-transporting ATP synthase activity, rotational mechanism.
Solver output
atp-3 encodes the oligomycin sensitivity conferral protein (OSCP), a subunit of the mitochondrial ATP synthase (Complex V) stator stalk that couples proton translocation across the inner mitochondrial membrane to ATP synthesis via a rotational mechanism. Paradoxically, in C. elegans, partial loss-of-function of mitochondrial electron transport chain and ATP synthase components (including atp-3 RNAi) has been shown to extend lifespan through mitohormesis — a mild mitochondrial stress signal that activates compensatory pathways such as the mitochondrial unfolded protein response (UPRmt) and reduced insulin/IGF-1 signaling. However, the normal (wild-type) function of atp-3 is to maximize oxidative phosphorylation efficiency and ATP production, which supports cellular energy homeostasis but also drives reactive oxygen species generation and aging. The pro-longevity effect is associated with its reduction, not its normal activity, making the wild-type function itself ambiguous with respect to longevity direction. Thus, the normal function of atp-3 neither clearly promotes nor opposes longevity without additional context about expression level and genetic background.
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 identifies the mechanistic context — atp-3 encodes OSCP, a subunit of mitochondrial ATP synthase, and correctly notes that RNAi knockdown of atp-3 can extend lifespan via mitohormesis. However, the ground truth classifies atp-3 as "anti_longevity," meaning its normal wild-type function promotes aging (i.e., loss of function extends life). The model's reasoning actually touches on this correctly but then hedges excessively, concluding "unclear" rather than committing to anti_longevity. The model understood the biology well enough to reach the right conclusion but failed to do so, instead choosing an overly cautious "unclear" classification with only 0.45 confidence. The mechanistic reasoning is sound but the final answer is wrong due to over-hedging.
Raw API responses
solver
{
"reasoning": "atp-3 encodes the oligomycin sensitivity conferral protein (OSCP), a subunit of the mitochondrial ATP synthase (Complex V) stator stalk that couples proton translocation across the inner mitochondrial membrane to ATP synthesis via a rotational mechanism. Paradoxically, in C. elegans, partial loss-of-function of mitochondrial electron transport chain and ATP synthase components (including atp-3 RNAi) has been shown to extend lifespan through mitohormesis — a mild mitochondrial stress signal that activates compensatory pathways such as the mitochondrial unfolded protein response (UPRmt) and reduced insulin/IGF-1 signaling. However, the normal (wild-type) function of atp-3 is to maximize oxidative phosphorylation efficiency and ATP production, which supports cellular energy homeostasis but also drives reactive oxygen species generation and aging. The pro-longevity effect is associated with its reduction, not its normal activity, making the wild-type function itself ambiguous with respect to longevity direction. Thus, the normal function of atp-3 neither clearly promotes nor opposes longevity without additional context about expression level and genetic background.",
"confidence": 0.45,
"key_pathways": [
"mitochondrial oxidative phosphorylation (Complex V / ATP synthase)",
"mitohormesis / mitochondrial unfolded protein response (UPRmt)",
"reactive oxygen species signaling"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "unclear"
}advisor
{
"notes": "The model correctly identifies the mechanistic context — atp-3 encodes OSCP, a subunit of mitochondrial ATP synthase, and correctly notes that RNAi knockdown of atp-3 can extend lifespan via mitohormesis. However, the ground truth classifies atp-3 as \"anti_longevity,\" meaning its normal wild-type function promotes aging (i.e., loss of function extends life). The model's reasoning actually touches on this correctly but then hedges excessively, concluding \"unclear\" rather than committing to anti_longevity. The model understood the biology well enough to reach the right conclusion but failed to do so, instead choosing an overly cautious \"unclear\" classification with only 0.45 confidence. The mechanistic reasoning is sound but the final answer is wrong due to over-hedging.",
"failure_mode": "overhedged",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}