nd-20
D. melanogaster
NADH dehydrogenase (ubiquinone) 20 kDa subunit
What the model saw
Gene: ND-20 Organism: Drosophila melanogaster Known functions: NADH dehydrogenase (ubiquinone) 20 kDa subunit. 4 iron, 4 sulfur cluster binding. NADH dehydrogenase (ubiquinone) activity. iron-sulfur cluster binding. quinone binding.
View unredacted entry
NADH dehydrogenase (ubiquinone) 20 kDa subunit. 4 iron, 4 sulfur cluster binding. NADH dehydrogenase (ubiquinone) activity. iron-sulfur cluster binding. quinone binding.
Solver output
ND-20 encodes the 20 kDa subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase), the first and largest enzyme of the electron transport chain. Its [4Fe-4S] cluster and quinone-binding activities are 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 typically impair mitochondrial respiration, increase ROS production, and shorten lifespan, consistent with a pro-longevity role for the wild-type gene. However, paradoxically, mild Complex I impairment has been shown in some contexts to extend lifespan via hormesis, introducing some uncertainty.
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 mechanistic reasoning about Complex I function, ROS production, and electron transport is generally sound. The model correctly identified that loss-of-function mutations in Complex I subunits typically shorten lifespan, which would make the wild-type gene pro-longevity — but the GenAge database classifies ND-20 as anti_longevity, suggesting that overexpression or gain-of-function of this gene reduces lifespan, or that the gene's normal activity promotes aging. The model did acknowledge the paradox of mild Complex I impairment extending lifespan via hormesis, but ultimately chose the wrong direction. The confidence of 0.62 is moderate but still led to an incorrect answer.
Raw API responses
solver
{
"reasoning": "ND-20 encodes the 20 kDa subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase), the first and largest enzyme of the electron transport chain. Its [4Fe-4S] cluster and quinone-binding activities are 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 typically impair mitochondrial respiration, increase ROS production, and shorten lifespan, consistent with a pro-longevity role for the wild-type gene. However, paradoxically, mild Complex I impairment has been shown in some contexts to extend lifespan via hormesis, introducing some uncertainty.",
"confidence": 0.62,
"key_pathways": [
"Mitochondrial Complex I / NADH:ubiquinone oxidoreductase (electron transport chain)",
"Iron-sulfur cluster electron transfer",
"Oxidative phosphorylation and ROS homeostasis"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted \"pro_longevity\" but the ground truth is \"anti_longevity.\" The mechanistic reasoning about Complex I function, ROS production, and electron transport is generally sound. The model correctly identified that loss-of-function mutations in Complex I subunits typically shorten lifespan, which would make the wild-type gene pro-longevity — but the GenAge database classifies ND-20 as anti_longevity, suggesting that overexpression or gain-of-function of this gene reduces lifespan, or that the gene's normal activity promotes aging. The model did acknowledge the paradox of mild Complex I impairment extending lifespan via hormesis, but ultimately chose the wrong direction. The confidence of 0.62 is moderate but still led to an incorrect answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}