NDE1
S. cerevisiae
NADH-ubiquinone reductase (H(+)-translocating) NDE1
What the model saw
Gene: NDE1 Organism: Saccharomyces cerevisiae Known functions: NADH-ubiquinone reductase (H(+)-translocating) NDE1. NADH dehydrogenase (quinone) (non-electrogenic) activity. NADH dehydrogenase (ubiquinone) (non-electrogenic) activity. NADH dehydrogenase activity. oxidoreductase activity.
View unredacted entry
NADH-ubiquinone reductase (H(+)-translocating) NDE1. NADH dehydrogenase (quinone) (non-electrogenic) activity. NADH dehydrogenase (ubiquinone) (non-electrogenic) activity. NADH dehydrogenase activity. oxidoreductase activity.
Solver output
NDE1 encodes the external NADH dehydrogenase on the outer face of the inner mitochondrial membrane in S. cerevisiae, which oxidizes cytosolic NADH and feeds electrons into the ubiquinone pool of the respiratory chain. By maintaining cytosolic NAD+/NADH redox balance and supporting mitochondrial electron transport chain flux, NDE1 promotes efficient oxidative phosphorylation without proton translocation (non-electrogenic). Proper mitochondrial respiratory function is a well-established determinant of yeast chronological and replicative lifespan; loss of respiratory capacity accelerates aging. Sustaining NADH oxidation via NDE1 prevents reductive stress and supports mitochondrial membrane potential indirectly through ubiquinol regeneration, both of which are associated with extended lifespan in yeast. Therefore, the normal function of NDE1 supports mitochondrial health and is predicted to be 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" with 0.72 confidence, but the ground truth is "unclear." The model constructed a plausible-sounding mechanistic argument about NDE1's role in NADH oxidation and mitochondrial function, but this reasoning is speculative and not supported by actual experimental evidence in GenAge. The model failed to account for the possibility that NDE1's role in longevity is genuinely ambiguous or that deletion studies may have shown mixed or unclear results. The confidence level (0.72) is inappropriately high given the actual unclear status. The mechanistic reasoning, while biochemically coherent in isolation, does not correctly predict the longevity influence as established by experimental evidence.
Raw API responses
solver
{
"reasoning": "NDE1 encodes the external NADH dehydrogenase on the outer face of the inner mitochondrial membrane in S. cerevisiae, which oxidizes cytosolic NADH and feeds electrons into the ubiquinone pool of the respiratory chain. By maintaining cytosolic NAD+/NADH redox balance and supporting mitochondrial electron transport chain flux, NDE1 promotes efficient oxidative phosphorylation without proton translocation (non-electrogenic). Proper mitochondrial respiratory function is a well-established determinant of yeast chronological and replicative lifespan; loss of respiratory capacity accelerates aging. Sustaining NADH oxidation via NDE1 prevents reductive stress and supports mitochondrial membrane potential indirectly through ubiquinol regeneration, both of which are associated with extended lifespan in yeast. Therefore, the normal function of NDE1 supports mitochondrial health and is predicted to be pro-longevity.",
"confidence": 0.72,
"key_pathways": [
"mitochondrial electron transport chain (Complex I-equivalent, external NADH oxidation)",
"NAD+/NADH redox homeostasis",
"ubiquinone/ubiquinol cycling"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted \"pro_longevity\" with 0.72 confidence, but the ground truth is \"unclear.\" The model constructed a plausible-sounding mechanistic argument about NDE1's role in NADH oxidation and mitochondrial function, but this reasoning is speculative and not supported by actual experimental evidence in GenAge. The model failed to account for the possibility that NDE1's role in longevity is genuinely ambiguous or that deletion studies may have shown mixed or unclear results. The confidence level (0.72) is inappropriately high given the actual unclear status. The mechanistic reasoning, while biochemically coherent in isolation, does not correctly predict the longevity influence as established by experimental evidence.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}