atg-9
C. elegans
Autophagy-related protein 9
What the model saw
Gene: atg-9 Organism: Caenorhabditis elegans Known functions: Autophagy-related protein 9. phospholipid scramblase activity.
View unredacted entry
Autophagy-related protein 9. phospholipid scramblase activity.
Solver output
ATG-9 is the sole transmembrane protein in the core autophagy machinery and is essential for autophagosome biogenesis. Its phospholipid scramblase activity facilitates lipid redistribution across membrane leaflets, directly supplying phospholipids to the expanding phagophore membrane during autophagosome formation. In C. elegans, functional autophagy is required for lifespan extension downstream of multiple longevity pathways including DAF-16/FOXO, dietary restriction, and mitochondrial stress. Loss of atg-9 impairs autophagic flux, leading to accumulation of damaged proteins and organelles — a hallmark of aging. Thus, the normal function of ATG-9 promotes autophagy-mediated proteostasis and organelle quality control, supporting longevity.
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 pro_longevity for atg-9 in C. elegans with high confidence (0.85). The mechanistic reasoning is thorough and accurate: ATG-9 is indeed the sole transmembrane protein in the core autophagy machinery, its phospholipid scramblase activity is correctly described as facilitating lipid redistribution for phagophore membrane expansion, and the connection to longevity pathways (DAF-16/FOXO, dietary restriction, mitochondrial stress) is well-established in the literature. The model correctly identifies that loss of atg-9 impairs autophagic flux and leads to accumulation of damaged proteins/organelles. The reasoning is detailed, mechanistically sound, and well-connected to the known biology of autophagy in C. elegans longevity.
Raw API responses
solver
{
"reasoning": "ATG-9 is the sole transmembrane protein in the core autophagy machinery and is essential for autophagosome biogenesis. Its phospholipid scramblase activity facilitates lipid redistribution across membrane leaflets, directly supplying phospholipids to the expanding phagophore membrane during autophagosome formation. In C. elegans, functional autophagy is required for lifespan extension downstream of multiple longevity pathways including DAF-16/FOXO, dietary restriction, and mitochondrial stress. Loss of atg-9 impairs autophagic flux, leading to accumulation of damaged proteins and organelles — a hallmark of aging. Thus, the normal function of ATG-9 promotes autophagy-mediated proteostasis and organelle quality control, supporting longevity.",
"confidence": 0.85,
"key_pathways": [
"autophagosome biogenesis",
"phospholipid scrambling at phagophore membrane",
"DAF-16/FOXO longevity pathway"
],
"mechanism_class": "disabled_macroautophagy",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for atg-9 in C. elegans with high confidence (0.85). The mechanistic reasoning is thorough and accurate: ATG-9 is indeed the sole transmembrane protein in the core autophagy machinery, its phospholipid scramblase activity is correctly described as facilitating lipid redistribution for phagophore membrane expansion, and the connection to longevity pathways (DAF-16/FOXO, dietary restriction, mitochondrial stress) is well-established in the literature. The model correctly identifies that loss of atg-9 impairs autophagic flux and leads to accumulation of damaged proteins/organelles. The reasoning is detailed, mechanistically sound, and well-connected to the known biology of autophagy in C. elegans longevity.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}