eat-3
C. elegans
Dynamin-like GTPase OPA1, mitochondrial
What the model saw
Gene: eat-3 Organism: Caenorhabditis elegans Known functions: Dynamin-like GTPase OPA1, mitochondrial. GTP binding. GTPase activity. microtubule binding.
View unredacted entry
Dynamin-like GTPase OPA1, mitochondrial. GTP binding. GTPase activity. microtubule binding.
Solver output
eat-3 encodes the C. elegans ortholog of OPA1, a dynamin-like GTPase that mediates inner mitochondrial membrane fusion. Its GTPase activity drives IMM fusion, which is essential for maintaining mitochondrial network integrity, cristae morphology, and efficient oxidative phosphorylation. Proper mitochondrial fusion via eat-3/OPA1 supports mitochondrial quality control by enabling complementation of damaged mitochondrial components and preventing accumulation of dysfunctional mitochondria. In C. elegans, mitochondrial fusion is linked to longevity pathways; partial loss of eat-3 can paradoxically extend lifespan through mitohormesis, but the normal function of eat-3 in sustaining mitochondrial integrity and bioenergetics is fundamentally pro-longevity. The microtubule-binding activity further supports mitochondrial distribution and network dynamics, reinforcing its role in maintaining healthy mitochondrial function over the organism's lifespan.
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 "pro_longevity" with 0.72 confidence, but the ground truth is "anti_longevity." eat-3/OPA1 loss-of-function in C. elegans is known to extend lifespan through mitohormesis, meaning eat-3 normally acts as an anti-longevity gene (its normal function suppresses longevity). The model actually acknowledged this paradox ("partial loss of eat-3 can paradoxically extend lifespan through mitohormesis") but then incorrectly concluded that the gene's "normal function" makes it pro-longevity. This is backwards: GenAge classifies genes by whether their loss/reduction extends lifespan (anti_longevity) or shortens it (pro_longevity). Since reducing eat-3 extends lifespan, eat-3 is anti_longevity. The model's mechanistic reasoning about OPA1's role in mitochondrial fusion is partially correct, but the interpretation of what that means for longevity classification is wrong. The model had the right information but drew the wrong conclusion.
Raw API responses
solver
{
"reasoning": "eat-3 encodes the C. elegans ortholog of OPA1, a dynamin-like GTPase that mediates inner mitochondrial membrane fusion. Its GTPase activity drives IMM fusion, which is essential for maintaining mitochondrial network integrity, cristae morphology, and efficient oxidative phosphorylation. Proper mitochondrial fusion via eat-3/OPA1 supports mitochondrial quality control by enabling complementation of damaged mitochondrial components and preventing accumulation of dysfunctional mitochondria. In C. elegans, mitochondrial fusion is linked to longevity pathways; partial loss of eat-3 can paradoxically extend lifespan through mitohormesis, but the normal function of eat-3 in sustaining mitochondrial integrity and bioenergetics is fundamentally pro-longevity. The microtubule-binding activity further supports mitochondrial distribution and network dynamics, reinforcing its role in maintaining healthy mitochondrial function over the organism's lifespan.",
"confidence": 0.72,
"key_pathways": [
"mitochondrial inner membrane fusion (IMM fusion)",
"mitochondrial quality control / mitophagy",
"mitohormesis / retrograde mitochondrial signaling"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted \"pro_longevity\" with 0.72 confidence, but the ground truth is \"anti_longevity.\" eat-3/OPA1 loss-of-function in C. elegans is known to extend lifespan through mitohormesis, meaning eat-3 normally acts as an anti-longevity gene (its normal function suppresses longevity). The model actually acknowledged this paradox (\"partial loss of eat-3 can paradoxically extend lifespan through mitohormesis\") but then incorrectly concluded that the gene's \"normal function\" makes it pro-longevity. This is backwards: GenAge classifies genes by whether their loss/reduction extends lifespan (anti_longevity) or shortens it (pro_longevity). Since reducing eat-3 extends lifespan, eat-3 is anti_longevity. The model's mechanistic reasoning about OPA1's role in mitochondrial fusion is partially correct, but the interpretation of what that means for longevity classification is wrong. The model had the right information but drew the wrong conclusion.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}