ATP3

S. cerevisiae

F1F0 ATP synthase subunit gamma

What the model saw

Gene: ATP3
Organism: Saccharomyces cerevisiae
Known functions: F1F0 ATP synthase subunit gamma. proton-transporting ATP synthase activity, rotational mechanism. proton-transporting ATPase activity, rotational mechanism.

View unredacted entry

F1F0 ATP synthase subunit gamma. proton-transporting ATP synthase activity, rotational mechanism. proton-transporting ATPase activity, rotational mechanism.

Solver output

Predicted influence

Pro-longevity

Confidence

82%

Mechanism

Mitochondrial dysfunction

Reasoning

ATP3 encodes the gamma subunit of the mitochondrial F1F0 ATP synthase in S. cerevisiae, which is the central rotating subunit that couples proton translocation across the inner mitochondrial membrane to ATP synthesis via the rotational catalytic mechanism. Proper function of this subunit is essential for oxidative phosphorylation efficiency and maintenance of the mitochondrial membrane potential. Loss or dysfunction of ATP synthase subunits leads to impaired mitochondrial bioenergetics, increased reactive oxygen species production, and accelerated aging phenotypes in yeast. Functional ATP synthase is also required for maintaining mitochondrial cristae morphology and the mitochondrial network, both of which are critical for yeast replicative and chronological lifespan. Therefore, the normal pro-oxidative phosphorylation activity of ATP3 supports mitochondrial health and opposes aging-associated mitochondrial dysfunction.

Key pathways

oxidative phosphorylation / F1F0 ATP synthase rotational catalysismitochondrial membrane potential maintenancemitochondrial cristae morphology and biogenesis

Longevity influence

Anti-longevity

Lifespan effect

Increase

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

Answer

✗Incorrect

Mechanism

✗Incorrect

Reasoning quality

2/5

Failure mode

Confident wrong

Notes

The model predicted pro_longevity with 0.82 confidence, but the ground truth is anti_longevity. The model's reasoning is based on the general logic that ATP synthase function supports mitochondrial health and therefore opposes aging — a plausible but ultimately incorrect inference. In yeast, ATP3 (F1F0 ATP synthase gamma subunit) is actually anti-longevity, meaning its deletion or loss of function extends lifespan. This is consistent with findings in the mitochondrial hormesis / retrograde signaling literature, where reduced OXPHOS activity can paradoxically extend lifespan in yeast (e.g., through caloric restriction-like effects, reduced ROS production under certain conditions, or retrograde signaling). The model failed to account for this nuance and instead applied a naive "more mitochondrial function = longer life" heuristic, which is incorrect here. The high confidence (0.82) makes this a notably wrong prediction.

Raw API responses

solver

{
  "reasoning": "ATP3 encodes the gamma subunit of the mitochondrial F1F0 ATP synthase in S. cerevisiae, which is the central rotating subunit that couples proton translocation across the inner mitochondrial membrane to ATP synthesis via the rotational catalytic mechanism. Proper function of this subunit is essential for oxidative phosphorylation efficiency and maintenance of the mitochondrial membrane potential. Loss or dysfunction of ATP synthase subunits leads to impaired mitochondrial bioenergetics, increased reactive oxygen species production, and accelerated aging phenotypes in yeast. Functional ATP synthase is also required for maintaining mitochondrial cristae morphology and the mitochondrial network, both of which are critical for yeast replicative and chronological lifespan. Therefore, the normal pro-oxidative phosphorylation activity of ATP3 supports mitochondrial health and opposes aging-associated mitochondrial dysfunction.",
  "confidence": 0.82,
  "key_pathways": [
    "oxidative phosphorylation / F1F0 ATP synthase rotational catalysis",
    "mitochondrial membrane potential maintenance",
    "mitochondrial cristae morphology and biogenesis"
  ],
  "mechanism_class": "mitochondrial_dysfunction",
  "longevity_influence": "pro_longevity"
}

advisor

{
  "notes": "The model predicted pro_longevity with 0.82 confidence, but the ground truth is anti_longevity. The model's reasoning is based on the general logic that ATP synthase function supports mitochondrial health and therefore opposes aging — a plausible but ultimately incorrect inference. In yeast, ATP3 (F1F0 ATP synthase gamma subunit) is actually anti-longevity, meaning its deletion or loss of function extends lifespan. This is consistent with findings in the mitochondrial hormesis / retrograde signaling literature, where reduced OXPHOS activity can paradoxically extend lifespan in yeast (e.g., through caloric restriction-like effects, reduced ROS production under certain conditions, or retrograde signaling). The model failed to account for this nuance and instead applied a naive \"more mitochondrial function = longer life\" heuristic, which is incorrect here. The high confidence (0.82) makes this a notably wrong prediction.",
  "failure_mode": "confident_wrong",
  "answer_correct": false,
  "mechanism_correct": false,
  "reasoning_quality": 2,
  "ground_truth_questionable": false
}