atp-5
C. elegans
ATP synthase subunit d, mitochondrial
What the model saw
Gene: atp-5 Organism: Caenorhabditis elegans Known functions: ATP synthase subunit d, mitochondrial. proton transmembrane transporter activity. proton-transporting ATP synthase activity, rotational mechanism.
View unredacted entry
ATP synthase subunit d, mitochondrial. proton transmembrane transporter activity. proton-transporting ATP synthase activity, rotational mechanism.
Solver output
atp-5 encodes the mitochondrial ATP synthase subunit d (part of the F0 stator subcomplex), which is essential for the rotational mechanism coupling proton translocation across the inner mitochondrial membrane to ATP synthesis. In C. elegans, the relationship between ATP synthase activity and longevity is paradoxical: partial loss-of-function of ATP synthase subunits (e.g., asb-2/atp-3) can extend lifespan via mitochondrial hormesis or reduced electron transport chain activity, mimicking dietary restriction. However, the normal function of atp-5 is to sustain efficient oxidative phosphorylation and ATP production, which is essential for cellular energy homeostasis. Full loss of ATP synthase function is lethal, while partial reduction can be pro-longevity, making the normal (wild-type) function of this gene neither clearly pro- nor anti-longevity in the context of aging hallmarks. The dual role of mitochondrial efficiency—supporting cellular function but also driving ROS production and potentially accelerating aging—makes a definitive directional call difficult for the wild-type gene product.
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 "unclear" while the ground truth is "anti_longevity." The model correctly identified the paradoxical nature of ATP synthase subunit knockdowns in C. elegans (partial loss can extend lifespan via mitohormesis), and its mechanistic reasoning is sound. However, it failed to commit to the correct directional call. The ground truth classifies atp-5 as anti_longevity, meaning the wild-type gene promotes aging (or its loss extends lifespan). The model was aware of this possibility but hedged too much, landing on "unclear" with only 0.45 confidence. The mechanistic reasoning about mitohormesis and partial loss-of-function extending lifespan is actually consistent with an anti_longevity classification for the wild-type gene, but the model didn't connect these dots to make the correct call.
Raw API responses
solver
{
"reasoning": "atp-5 encodes the mitochondrial ATP synthase subunit d (part of the F0 stator subcomplex), which is essential for the rotational mechanism coupling proton translocation across the inner mitochondrial membrane to ATP synthesis. In C. elegans, the relationship between ATP synthase activity and longevity is paradoxical: partial loss-of-function of ATP synthase subunits (e.g., asb-2/atp-3) can extend lifespan via mitochondrial hormesis or reduced electron transport chain activity, mimicking dietary restriction. However, the normal function of atp-5 is to sustain efficient oxidative phosphorylation and ATP production, which is essential for cellular energy homeostasis. Full loss of ATP synthase function is lethal, while partial reduction can be pro-longevity, making the normal (wild-type) function of this gene neither clearly pro- nor anti-longevity in the context of aging hallmarks. The dual role of mitochondrial efficiency—supporting cellular function but also driving ROS production and potentially accelerating aging—makes a definitive directional call difficult for the wild-type gene product.",
"confidence": 0.45,
"key_pathways": [
"oxidative phosphorylation / ATP synthesis",
"mitochondrial proton gradient (chemiosmosis)",
"mitochondrial hormesis (mitohormesis)"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "unclear"
}advisor
{
"notes": "The model predicted \"unclear\" while the ground truth is \"anti_longevity.\" The model correctly identified the paradoxical nature of ATP synthase subunit knockdowns in C. elegans (partial loss can extend lifespan via mitohormesis), and its mechanistic reasoning is sound. However, it failed to commit to the correct directional call. The ground truth classifies atp-5 as anti_longevity, meaning the wild-type gene promotes aging (or its loss extends lifespan). The model was aware of this possibility but hedged too much, landing on \"unclear\" with only 0.45 confidence. The mechanistic reasoning about mitohormesis and partial loss-of-function extending lifespan is actually consistent with an anti_longevity classification for the wild-type gene, but the model didn't connect these dots to make the correct call.",
"failure_mode": "appropriately_uncertain",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}