nuo-5
C. elegans
NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial
What the model saw
Gene: nuo-5 Organism: Caenorhabditis elegans Known functions: NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial. NADH dehydrogenase (ubiquinone) activity. iron-sulfur cluster binding. oxidoreductase activity. oxidoreductase activity, acting on NAD(P)H.
View unredacted entry
NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial. NADH dehydrogenase (ubiquinone) activity. iron-sulfur cluster binding. oxidoreductase activity. oxidoreductase activity, acting on NAD(P)H.
Solver output
nuo-5 encodes the 75 kDa iron-sulfur (NUFS1) subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase), which catalyzes the first and rate-limiting step of the mitochondrial electron transport chain — transferring electrons from NADH to ubiquinone via iron-sulfur clusters. In C. elegans, partial loss-of-function of Complex I subunits (including nuo-5/NDUFS1) is well-documented to extend lifespan, likely through mild mitochondrial stress (mitohormesis) that activates the mitochondrial unfolded protein response (UPRmt) and reduces reactive oxygen species flux. However, the gene's normal (wild-type) function is to sustain full Complex I activity, which supports ATP production and organismal fitness. Because reduced Complex I activity — not its normal full activity — is what extends lifespan in this organism, the wild-type function of nuo-5 (maintaining maximal Complex I throughput) is paradoxically associated with a shorter lifespan relative to partial loss-of-function states, placing it in the anti-longevity category under normal function. Nonetheless, complete loss is lethal, indicating the gene is essential; the longevity benefit arises only from partial reduction, making the overall influence of its normal function modestly anti-longevity via the mitochondrial dysfunction/mitohormesis axis.
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 identified the mechanism (Complex I subunit, mitohormesis, UPRmt, partial loss-of-function extends lifespan) but arrived at the wrong final answer. The ground truth is "anti_longevity," meaning the wild-type gene's normal function is anti-longevity (i.e., its knockdown/reduction extends lifespan). The model's reasoning actually correctly describes this anti_longevity logic in the latter part of its reasoning, yet it labeled the prediction as "pro_longevity" (confidence 0.62). This is a contradiction within the model's own reasoning — the mechanistic explanation supports anti_longevity, but the final classification label says pro_longevity. The model essentially talked itself into the correct answer mechanistically but then submitted the wrong label.
Raw API responses
solver
{
"reasoning": "nuo-5 encodes the 75 kDa iron-sulfur (NUFS1) subunit of mitochondrial Complex I (NADH:ubiquinone oxidoreductase), which catalyzes the first and rate-limiting step of the mitochondrial electron transport chain — transferring electrons from NADH to ubiquinone via iron-sulfur clusters. In C. elegans, partial loss-of-function of Complex I subunits (including nuo-5/NDUFS1) is well-documented to extend lifespan, likely through mild mitochondrial stress (mitohormesis) that activates the mitochondrial unfolded protein response (UPRmt) and reduces reactive oxygen species flux. However, the gene's normal (wild-type) function is to sustain full Complex I activity, which supports ATP production and organismal fitness. Because reduced Complex I activity — not its normal full activity — is what extends lifespan in this organism, the wild-type function of nuo-5 (maintaining maximal Complex I throughput) is paradoxically associated with a shorter lifespan relative to partial loss-of-function states, placing it in the anti-longevity category under normal function. Nonetheless, complete loss is lethal, indicating the gene is essential; the longevity benefit arises only from partial reduction, making the overall influence of its normal function modestly anti-longevity via the mitochondrial dysfunction/mitohormesis axis.",
"confidence": 0.62,
"key_pathways": [
"mitochondrial electron transport chain (Complex I)",
"mitohormesis / mitochondrial unfolded protein response (UPRmt)",
"NAD+/NADH redox balance and oxidative phosphorylation"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identified the mechanism (Complex I subunit, mitohormesis, UPRmt, partial loss-of-function extends lifespan) but arrived at the wrong final answer. The ground truth is \"anti_longevity,\" meaning the wild-type gene's normal function is anti-longevity (i.e., its knockdown/reduction extends lifespan). The model's reasoning actually correctly describes this anti_longevity logic in the latter part of its reasoning, yet it labeled the prediction as \"pro_longevity\" (confidence 0.62). This is a contradiction within the model's own reasoning — the mechanistic explanation supports anti_longevity, but the final classification label says pro_longevity. The model essentially talked itself into the correct answer mechanistically but then submitted the wrong label.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}