nnt-1
C. elegans
NAD(P) transhydrogenase, mitochondrial
What the model saw
Gene: nnt-1 Organism: Caenorhabditis elegans Known functions: NAD(P) transhydrogenase, mitochondrial. NADP binding. proton-translocating NAD(P)+ transhydrogenase activity.
View unredacted entry
NAD(P) transhydrogenase, mitochondrial. NADP binding. proton-translocating NAD(P)+ transhydrogenase activity.
Solver output
NNT-1 encodes the mitochondrial nicotinamide nucleotide transhydrogenase, which uses the proton electrochemical gradient across the inner mitochondrial membrane to drive the reduction of NADP+ to NADPH using NADH as the electron donor. This reaction is a primary source of mitochondrial NADPH, which is essential for regenerating reduced glutathione and thioredoxin via glutathione reductase and thioredoxin reductase, respectively. Adequate mitochondrial NADPH is therefore critical for neutralizing mitochondrial reactive oxygen species (ROS) and maintaining redox homeostasis. Loss of NNT function leads to elevated mitochondrial oxidative stress, which is a well-established driver of mitochondrial dysfunction and accelerated aging. By sustaining the mitochondrial antioxidant defense system, NNT-1 supports mitochondrial integrity and opposes the accumulation of oxidative damage associated with aging in C. elegans.
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 predicted pro_longevity for nnt-1 in C. elegans. The mechanistic reasoning is sound and well-grounded: NNT-1 produces mitochondrial NADPH via the proton gradient, which supports antioxidant defenses (glutathione/thioredoxin systems), thereby reducing oxidative stress and supporting longevity. This is a well-established mechanism for NNT function. The confidence of 0.72 is reasonable. The reasoning is coherent and biologically accurate, though it could have been strengthened by citing specific C. elegans experimental evidence (e.g., RNAi knockdown studies showing reduced lifespan). Overall a strong prediction with correct answer and correct mechanism.
Raw API responses
solver
{
"reasoning": "NNT-1 encodes the mitochondrial nicotinamide nucleotide transhydrogenase, which uses the proton electrochemical gradient across the inner mitochondrial membrane to drive the reduction of NADP+ to NADPH using NADH as the electron donor. This reaction is a primary source of mitochondrial NADPH, which is essential for regenerating reduced glutathione and thioredoxin via glutathione reductase and thioredoxin reductase, respectively. Adequate mitochondrial NADPH is therefore critical for neutralizing mitochondrial reactive oxygen species (ROS) and maintaining redox homeostasis. Loss of NNT function leads to elevated mitochondrial oxidative stress, which is a well-established driver of mitochondrial dysfunction and accelerated aging. By sustaining the mitochondrial antioxidant defense system, NNT-1 supports mitochondrial integrity and opposes the accumulation of oxidative damage associated with aging in C. elegans.",
"confidence": 0.72,
"key_pathways": [
"mitochondrial NADPH production",
"glutathione/thioredoxin antioxidant system",
"mitochondrial redox homeostasis"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for nnt-1 in C. elegans. The mechanistic reasoning is sound and well-grounded: NNT-1 produces mitochondrial NADPH via the proton gradient, which supports antioxidant defenses (glutathione/thioredoxin systems), thereby reducing oxidative stress and supporting longevity. This is a well-established mechanism for NNT function. The confidence of 0.72 is reasonable. The reasoning is coherent and biologically accurate, though it could have been strengthened by citing specific C. elegans experimental evidence (e.g., RNAi knockdown studies showing reduced lifespan). Overall a strong prediction with correct answer and correct mechanism.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}