PHB2
S. cerevisiae
prohibitin subunit PHB2
What the model saw
Gene: PHB2 Organism: Saccharomyces cerevisiae Known functions: prohibitin subunit PHB2. mitochondrion autophagosome adaptor activity. protein binding.
View unredacted entry
prohibitin subunit PHB2. mitochondrion autophagosome adaptor activity. protein binding.
Solver output
PHB2 is a core subunit of the prohibitin complex (PHB1/PHB2), which resides in the inner mitochondrial membrane and is essential for mitochondrial membrane integrity, cristae organization, and mitochondrial quality control. Its annotated function as a "mitochondrion autophagosome adaptor" indicates a direct role in mitophagy — the selective autophagic degradation of damaged mitochondria — by acting as a receptor that links mitochondria to the autophagosome machinery. Efficient mitophagy is critical for clearing dysfunctional mitochondria, thereby preventing the accumulation of ROS and mitochondrial damage that drives aging. In yeast, prohibitin complex integrity is required for normal replicative and chronological lifespan, and loss of PHB2 leads to mitochondrial dysfunction and shortened lifespan. By facilitating mitophagy adaptor activity, PHB2 supports both mitochondrial quality and autophagic flux, two processes whose decline is a hallmark of 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 PHB2 as pro_longevity in S. cerevisiae. The mechanistic reasoning is solid and well-grounded: PHB2 as part of the prohibitin complex is indeed involved in mitochondrial quality control, inner membrane integrity, and mitophagy. The model correctly identifies that loss of PHB2 leads to mitochondrial dysfunction and shortened lifespan. The mechanism_class "disabled_macroautophagy" is a bit oddly named for what is described (it seems to be describing the gene's role in enabling mitophagy rather than disabling macroautophagy), but the underlying reasoning about mitophagy adaptor activity and mitochondrial quality control is appropriate. The confidence of 0.78 is reasonable. Minor issue: the mechanism_class label doesn't perfectly match the described mechanism, but the textual reasoning is coherent and accurate.
Raw API responses
solver
{
"reasoning": "PHB2 is a core subunit of the prohibitin complex (PHB1/PHB2), which resides in the inner mitochondrial membrane and is essential for mitochondrial membrane integrity, cristae organization, and mitochondrial quality control. Its annotated function as a \"mitochondrion autophagosome adaptor\" indicates a direct role in mitophagy — the selective autophagic degradation of damaged mitochondria — by acting as a receptor that links mitochondria to the autophagosome machinery. Efficient mitophagy is critical for clearing dysfunctional mitochondria, thereby preventing the accumulation of ROS and mitochondrial damage that drives aging. In yeast, prohibitin complex integrity is required for normal replicative and chronological lifespan, and loss of PHB2 leads to mitochondrial dysfunction and shortened lifespan. By facilitating mitophagy adaptor activity, PHB2 supports both mitochondrial quality and autophagic flux, two processes whose decline is a hallmark of aging.",
"confidence": 0.78,
"key_pathways": [
"mitophagy / selective autophagy",
"prohibitin complex-mediated mitochondrial quality control",
"mitochondrial inner membrane organization"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted PHB2 as pro_longevity in S. cerevisiae. The mechanistic reasoning is solid and well-grounded: PHB2 as part of the prohibitin complex is indeed involved in mitochondrial quality control, inner membrane integrity, and mitophagy. The model correctly identifies that loss of PHB2 leads to mitochondrial dysfunction and shortened lifespan. The mechanism_class \"disabled_macroautophagy\" is a bit oddly named for what is described (it seems to be describing the gene's role in enabling mitophagy rather than disabling macroautophagy), but the underlying reasoning about mitophagy adaptor activity and mitochondrial quality control is appropriate. The confidence of 0.78 is reasonable. Minor issue: the mechanism_class label doesn't perfectly match the described mechanism, but the textual reasoning is coherent and accurate.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}