nuo-1
C. elegans
NADH dehydrogenase
What the model saw
Gene: nuo-1 Organism: Caenorhabditis elegans Known functions: NADH dehydrogenase. 4 iron, 4 sulfur cluster binding. FMN binding. NAD binding. NADH dehydrogenase (ubiquinone) activity.
View unredacted entry
NADH dehydrogenase. 4 iron, 4 sulfur cluster binding. FMN binding. NAD binding. NADH dehydrogenase (ubiquinone) activity.
Solver output
nuo-1 encodes the 51 kDa flavoprotein subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase), the entry point for electrons from NADH into the electron transport chain. Its FMN-binding and 4Fe-4S cluster-binding activities are essential for electron transfer from NADH to ubiquinone. In C. elegans, partial loss-of-function of Complex I subunits (e.g., via RNAi) is well-documented to extend lifespan, consistent with the mitohormesis model where mild mitochondrial electron transport chain impairment reduces ROS production at Complex I and/or activates compensatory stress-response pathways (HIF-1, DAF-16). Full wild-type activity of nuo-1 therefore sustains maximal Complex I flux, which is associated with higher mitochondrial ROS output and shorter lifespan, making the normal function of this gene anti-longevity. The NAD-binding activity also links Complex I to the NAD⁺/NADH ratio, a key regulator of sirtuin activity and metabolic 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 correctly predicted anti_longevity for nuo-1. The mechanistic reasoning is excellent: it correctly identifies nuo-1 as the 51 kDa flavoprotein subunit of Complex I, explains the FMN and 4Fe-4S cluster roles in electron transfer, and correctly invokes the mitohormesis model where partial loss-of-function of Complex I subunits extends lifespan in C. elegans (meaning wild-type function is anti-longevity). The model also correctly notes the NAD+/NADH ratio connection. The confidence level of 0.72 is appropriate given the complexity of the relationship. All key pathways identified are relevant and accurate.
Raw API responses
solver
{
"reasoning": "nuo-1 encodes the 51 kDa flavoprotein subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase), the entry point for electrons from NADH into the electron transport chain. Its FMN-binding and 4Fe-4S cluster-binding activities are essential for electron transfer from NADH to ubiquinone. In C. elegans, partial loss-of-function of Complex I subunits (e.g., via RNAi) is well-documented to extend lifespan, consistent with the mitohormesis model where mild mitochondrial electron transport chain impairment reduces ROS production at Complex I and/or activates compensatory stress-response pathways (HIF-1, DAF-16). Full wild-type activity of nuo-1 therefore sustains maximal Complex I flux, which is associated with higher mitochondrial ROS output and shorter lifespan, making the normal function of this gene anti-longevity. The NAD-binding activity also links Complex I to the NAD⁺/NADH ratio, a key regulator of sirtuin activity and metabolic aging.",
"confidence": 0.72,
"key_pathways": [
"Mitochondrial Complex I / electron transport chain",
"Mitohormesis / ROS signaling",
"NAD+/NADH redox balance"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for nuo-1. The mechanistic reasoning is excellent: it correctly identifies nuo-1 as the 51 kDa flavoprotein subunit of Complex I, explains the FMN and 4Fe-4S cluster roles in electron transfer, and correctly invokes the mitohormesis model where partial loss-of-function of Complex I subunits extends lifespan in C. elegans (meaning wild-type function is anti-longevity). The model also correctly notes the NAD+/NADH ratio connection. The confidence level of 0.72 is appropriate given the complexity of the relationship. All key pathways identified are relevant and accurate.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}