NDI1
S. cerevisiae
NADH-ubiquinone reductase (H(+)-translocating) NDI1
What the model saw
Gene: NDI1 Organism: Saccharomyces cerevisiae Known functions: NADH-ubiquinone reductase (H(+)-translocating) NDI1. NADH dehydrogenase (quinone) (non-electrogenic) activity. NADH dehydrogenase (ubiquinone) (non-electrogenic) activity. NADH dehydrogenase activity. identical protein binding. oxidoreductase activity.
View unredacted entry
NADH-ubiquinone reductase (H(+)-translocating) NDI1. NADH dehydrogenase (quinone) (non-electrogenic) activity. NADH dehydrogenase (ubiquinone) (non-electrogenic) activity. NADH dehydrogenase activity. identical protein binding. oxidoreductase activity.
Solver output
NDI1 encodes the internal NADH dehydrogenase of the yeast inner mitochondrial membrane, which oxidizes matrix NADH and transfers electrons to ubiquinone (CoQ) without pumping protons (non-electrogenic). By maintaining efficient electron flow through the respiratory chain, NDI1 supports mitochondrial membrane potential and ATP production while limiting electron leak and reactive oxygen species (ROS) generation. Proper NADH/NAD+ redox balance maintained by NDI1 is critical for TCA cycle flux and overall mitochondrial health. Overexpression of NDI1 in other organisms (e.g., Drosophila) has been shown to extend lifespan by improving mitochondrial function and reducing oxidative damage, consistent with a pro-longevity role. Loss of NDI1 function impairs mitochondrial respiration and increases oxidative stress, hallmarks of mitochondrial dysfunction associated with aging.
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" with high confidence (0.82), but the ground truth is "unclear." The model's reasoning draws heavily on NDI1's role in Drosophila (where overexpression extends lifespan), but this is a yeast entry and the evidence in S. cerevisiae is apparently ambiguous enough to be classified as "unclear." The model conflates cross-species evidence and presents it as strong support for a pro-longevity classification in yeast specifically. The mechanistic description of NDI1's biochemical function is accurate, but the leap to a confident pro-longevity classification is not supported by the available yeast-specific evidence. The model should have been more uncertain given the complexity of the evidence.
Raw API responses
solver
{
"reasoning": "NDI1 encodes the internal NADH dehydrogenase of the yeast inner mitochondrial membrane, which oxidizes matrix NADH and transfers electrons to ubiquinone (CoQ) without pumping protons (non-electrogenic). By maintaining efficient electron flow through the respiratory chain, NDI1 supports mitochondrial membrane potential and ATP production while limiting electron leak and reactive oxygen species (ROS) generation. Proper NADH/NAD+ redox balance maintained by NDI1 is critical for TCA cycle flux and overall mitochondrial health. Overexpression of NDI1 in other organisms (e.g., Drosophila) has been shown to extend lifespan by improving mitochondrial function and reducing oxidative damage, consistent with a pro-longevity role. Loss of NDI1 function impairs mitochondrial respiration and increases oxidative stress, hallmarks of mitochondrial dysfunction associated with aging.",
"confidence": 0.82,
"key_pathways": [
"mitochondrial electron transport chain (Complex I alternative)",
"NADH/NAD+ redox homeostasis",
"reactive oxygen species (ROS) management"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted \"pro_longevity\" with high confidence (0.82), but the ground truth is \"unclear.\" The model's reasoning draws heavily on NDI1's role in Drosophila (where overexpression extends lifespan), but this is a yeast entry and the evidence in S. cerevisiae is apparently ambiguous enough to be classified as \"unclear.\" The model conflates cross-species evidence and presents it as strong support for a pro-longevity classification in yeast specifically. The mechanistic description of NDI1's biochemical function is accurate, but the leap to a confident pro-longevity classification is not supported by the available yeast-specific evidence. The model should have been more uncertain given the complexity of the evidence.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}