nd-75
D. melanogaster
NADH dehydrogenase (ubiquinone) 75 kDa subunit
What the model saw
Gene: ND-75 Organism: Drosophila melanogaster Known functions: NADH dehydrogenase (ubiquinone) 75 kDa subunit. NADH dehydrogenase (ubiquinone) activity. iron-sulfur cluster binding. oxidoreductase activity. oxidoreductase activity, acting on NAD(P)H.
View unredacted entry
NADH dehydrogenase (ubiquinone) 75 kDa subunit. NADH dehydrogenase (ubiquinone) activity. iron-sulfur cluster binding. oxidoreductase activity. oxidoreductase activity, acting on NAD(P)H.
Solver output
ND-75 encodes the 75 kDa iron-sulfur (NDUFS1) subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase), the largest and first enzyme of the mitochondrial electron transport chain. Its iron-sulfur cluster binding activity is essential for electron transfer from NADH to ubiquinone, driving the proton gradient used for ATP synthesis. Proper Complex I function is critical for efficient oxidative phosphorylation and limiting electron leak that generates reactive oxygen species (ROS). Loss-of-function mutations in Complex I subunits in Drosophila are well-documented to increase mitochondrial ROS production, impair ATP generation, and shorten lifespan, consistent with the mitochondrial dysfunction hallmark of aging. Therefore, the normal (wild-type) function of ND-75 supports mitochondrial integrity and opposes premature aging, making it pro-longevity.
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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is based on the assumption that loss-of-function of Complex I subunits shortens lifespan, therefore the gene is pro_longevity. However, the GenAge classification of anti_longevity for ND-75 suggests that reduced expression or loss of function of this gene actually extends lifespan in Drosophila — consistent with the mitohormesis hypothesis or the idea that mild mitochondrial dysfunction (including reduced Complex I activity) can paradoxically extend lifespan by reducing ROS production or activating stress response pathways. The model's mechanistic reasoning about Complex I function is generally accurate, but it incorrectly applied the logic to conclude pro_longevity when the actual experimental evidence shows anti_longevity (i.e., the gene promotes aging rather than opposing it). The model was fairly confident (0.72) in its wrong answer.
Raw API responses
solver
{
"reasoning": "ND-75 encodes the 75 kDa iron-sulfur (NDUFS1) subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase), the largest and first enzyme of the mitochondrial electron transport chain. Its iron-sulfur cluster binding activity is essential for electron transfer from NADH to ubiquinone, driving the proton gradient used for ATP synthesis. Proper Complex I function is critical for efficient oxidative phosphorylation and limiting electron leak that generates reactive oxygen species (ROS). Loss-of-function mutations in Complex I subunits in Drosophila are well-documented to increase mitochondrial ROS production, impair ATP generation, and shorten lifespan, consistent with the mitochondrial dysfunction hallmark of aging. Therefore, the normal (wild-type) function of ND-75 supports mitochondrial integrity and opposes premature aging, making it pro-longevity.",
"confidence": 0.72,
"key_pathways": [
"mitochondrial electron transport chain (Complex I)",
"oxidative phosphorylation",
"iron-sulfur cluster assembly and electron transfer"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is based on the assumption that loss-of-function of Complex I subunits shortens lifespan, therefore the gene is pro_longevity. However, the GenAge classification of anti_longevity for ND-75 suggests that reduced expression or loss of function of this gene actually extends lifespan in Drosophila — consistent with the mitohormesis hypothesis or the idea that mild mitochondrial dysfunction (including reduced Complex I activity) can paradoxically extend lifespan by reducing ROS production or activating stress response pathways. The model's mechanistic reasoning about Complex I function is generally accurate, but it incorrectly applied the logic to conclude pro_longevity when the actual experimental evidence shows anti_longevity (i.e., the gene promotes aging rather than opposing it). The model was fairly confident (0.72) in its wrong answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}