nuo-4
C. elegans
Deoxynucleoside kinase domain-containing protein;NADH dehydrogenase
What the model saw
Gene: nuo-4 Organism: Caenorhabditis elegans Known functions: Deoxynucleoside kinase domain-containing protein;NADH dehydrogenase. NADH dehydrogenase (ubiquinone) activity.
View unredacted entry
Deoxynucleoside kinase domain-containing protein;NADH dehydrogenase. NADH dehydrogenase (ubiquinone) activity.
Solver output
nuo-4 encodes a subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase), the first and largest enzyme of the mitochondrial electron transport chain. Complex I activity drives proton pumping across the inner mitochondrial membrane and is a major source of reactive oxygen species (ROS) production. In C. elegans, partial loss-of-function of Complex I subunits (e.g., nuo-1, gas-1) is well-documented to extend lifespan via reduced electron transport chain activity, lowered ROS generation, and activation of mitohormesis signaling. Conversely, normal (full) Complex I function sustains high electron flux and ROS production, which accelerates oxidative damage and aging. Therefore, the wild-type pro-activity function of nuo-4 opposes longevity by maintaining maximal Complex I-driven mitochondrial respiration and associated oxidative stress.
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 anti_longevity for nuo-4. The mechanistic reasoning is sound: nuo-4 encodes a Complex I (NADH dehydrogenase) subunit, and loss-of-function of Complex I subunits in C. elegans is well-established to extend lifespan, making the wild-type gene anti-longevity. The model correctly cites analogous genes (nuo-1, gas-1) and the mitohormesis/ROS framework. The reasoning is slightly simplified (the mitohormesis story is more nuanced - reduced ETC activity extends lifespan partly through reduced ROS but also through other mechanisms like AMPK activation), but overall the mechanistic explanation is appropriate and well-supported. Confidence of 0.72 is reasonable.
Raw API responses
solver
{
"reasoning": "nuo-4 encodes a subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase), the first and largest enzyme of the mitochondrial electron transport chain. Complex I activity drives proton pumping across the inner mitochondrial membrane and is a major source of reactive oxygen species (ROS) production. In C. elegans, partial loss-of-function of Complex I subunits (e.g., nuo-1, gas-1) is well-documented to extend lifespan via reduced electron transport chain activity, lowered ROS generation, and activation of mitohormesis signaling. Conversely, normal (full) Complex I function sustains high electron flux and ROS production, which accelerates oxidative damage and aging. Therefore, the wild-type pro-activity function of nuo-4 opposes longevity by maintaining maximal Complex I-driven mitochondrial respiration and associated oxidative stress.",
"confidence": 0.72,
"key_pathways": [
"Mitochondrial electron transport chain (Complex I / NADH:ubiquinone oxidoreductase)",
"Reactive oxygen species (ROS) production and mitohormesis",
"Mitochondrial membrane potential and oxidative phosphorylation"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for nuo-4. The mechanistic reasoning is sound: nuo-4 encodes a Complex I (NADH dehydrogenase) subunit, and loss-of-function of Complex I subunits in C. elegans is well-established to extend lifespan, making the wild-type gene anti-longevity. The model correctly cites analogous genes (nuo-1, gas-1) and the mitohormesis/ROS framework. The reasoning is slightly simplified (the mitohormesis story is more nuanced - reduced ETC activity extends lifespan partly through reduced ROS but also through other mechanisms like AMPK activation), but overall the mechanistic explanation is appropriate and well-supported. Confidence of 0.72 is reasonable.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}