isp-1
C. elegans
Cytochrome b-c1 complex subunit Rieske, mitochondrial
What the model saw
Gene: isp-1 Organism: Caenorhabditis elegans Known functions: Cytochrome b-c1 complex subunit Rieske, mitochondrial. 2 iron, 2 sulfur cluster binding. oxidoreductase activity. quinol-cytochrome-c reductase activity.
View unredacted entry
Cytochrome b-c1 complex subunit Rieske, mitochondrial. 2 iron, 2 sulfur cluster binding. oxidoreductase activity. quinol-cytochrome-c reductase activity.
Solver output
isp-1 encodes the Rieske iron-sulfur protein subunit of mitochondrial Complex III (cytochrome bc1 complex), which catalyzes quinol-cytochrome-c reductase activity as part of the electron transport chain. Partial loss-of-function mutations in isp-1 reduce electron flow through Complex III, lowering mitochondrial membrane potential and ROS production while paradoxically extending lifespan in C. elegans — a well-characterized example of the "mitohormesis" phenomenon. The reduced ETC activity triggers compensatory stress responses (including HIF-1 and DAF-16/FOXO pathways) that enhance stress resistance and promote longevity. This places isp-1 in the category where its normal full activity is actually detrimental to longevity, meaning the wild-type gene function (maximal Complex III activity) is anti-longevity; however, since the gene's normal function sustains mitochondrial respiration and its reduction extends life, the gene's normal activity opposes longevity. Thus isp-1 normal function is anti-longevity via mitochondrial electron transport chain activity at Complex III.
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 biological mechanism: isp-1 encodes the Rieske iron-sulfur protein of Complex III, and loss-of-function mutations extend lifespan via mitohormesis. The mechanistic reasoning is accurate. However, the model contradicts itself in its final conclusion. It correctly reasons that "the wild-type gene function (maximal Complex III activity) is anti-longevity" but then outputs "pro_longevity" as its longevity_influence prediction. The ground truth is "anti_longevity." The model's reasoning actually arrives at the correct answer (anti_longevity) but the final prediction field says "pro_longevity," making this a case where the reasoning is correct but the final answer is wrong. This is a notable failure mode where the model's stated conclusion in the reasoning contradicts its submitted prediction label.
Raw API responses
solver
{
"reasoning": "isp-1 encodes the Rieske iron-sulfur protein subunit of mitochondrial Complex III (cytochrome bc1 complex), which catalyzes quinol-cytochrome-c reductase activity as part of the electron transport chain. Partial loss-of-function mutations in isp-1 reduce electron flow through Complex III, lowering mitochondrial membrane potential and ROS production while paradoxically extending lifespan in C. elegans — a well-characterized example of the \"mitohormesis\" phenomenon. The reduced ETC activity triggers compensatory stress responses (including HIF-1 and DAF-16/FOXO pathways) that enhance stress resistance and promote longevity. This places isp-1 in the category where its normal full activity is actually detrimental to longevity, meaning the wild-type gene function (maximal Complex III activity) is anti-longevity; however, since the gene's normal function sustains mitochondrial respiration and its reduction extends life, the gene's normal activity opposes longevity. Thus isp-1 normal function is anti-longevity via mitochondrial electron transport chain activity at Complex III.",
"confidence": 0.82,
"key_pathways": [
"mitochondrial electron transport chain (Complex III / cytochrome bc1)",
"mitohormesis / ROS signaling",
"DAF-16/FOXO stress response"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identifies the biological mechanism: isp-1 encodes the Rieske iron-sulfur protein of Complex III, and loss-of-function mutations extend lifespan via mitohormesis. The mechanistic reasoning is accurate. However, the model contradicts itself in its final conclusion. It correctly reasons that \"the wild-type gene function (maximal Complex III activity) is anti-longevity\" but then outputs \"pro_longevity\" as its longevity_influence prediction. The ground truth is \"anti_longevity.\" The model's reasoning actually arrives at the correct answer (anti_longevity) but the final prediction field says \"pro_longevity,\" making this a case where the reasoning is correct but the final answer is wrong. This is a notable failure mode where the model's stated conclusion in the reasoning contradicts its submitted prediction label.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}