atpcl
D. melanogaster
ATP citrate lyase
What the model saw
Gene: ATPCL Organism: Drosophila melanogaster Known functions: ATP citrate lyase. ATP binding. ATP citrate synthase activity. acyltransferase activity, acyl groups converted into alkyl on transfer. catalytic activity. metal ion binding.
View unredacted entry
ATP citrate lyase. ATP binding. ATP citrate synthase activity. acyltransferase activity, acyl groups converted into alkyl on transfer. catalytic activity. metal ion binding.
Solver output
ATP citrate lyase (ATPCL) cleaves citrate into acetyl-CoA and oxaloacetate in the cytoplasm, serving as the primary source of cytosolic acetyl-CoA. Cytosolic acetyl-CoA is the obligate substrate for histone acetyltransferases, directly linking nutrient/metabolic status to epigenetic regulation of gene expression. Adequate ATPCL activity supports histone acetylation homeostasis, which is critical for maintaining youthful transcriptional programs and chromatin accessibility. Loss of cytosolic acetyl-CoA supply leads to hypoacetylation of histones, a hallmark of epigenetic drift associated with aging. Additionally, acetyl-CoA produced by ATPCL feeds into lipid biosynthesis and protein acetylation, supporting broader anabolic and proteostatic functions that favor organismal health and 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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about ATPCL's biochemical role (cytosolic acetyl-CoA production via citrate cleavage) is mechanistically accurate, but the model incorrectly assumed that this activity promotes longevity. In reality, ATPCL is anti-longevity in Drosophila, meaning its activity shortens lifespan (or its reduction extends lifespan). The model's logic that "adequate ATPCL activity supports histone acetylation homeostasis" and thus promotes longevity is flawed in the context of this organism's aging biology. The model also incorrectly classified the mechanism as "epigenetic_alterations" when the anti-longevity effect likely involves metabolic dysregulation (e.g., excessive lipid synthesis, altered nutrient sensing). The model had moderate confidence (0.62) but was wrong on both the direction and the mechanistic framing.
Raw API responses
solver
{
"reasoning": "ATP citrate lyase (ATPCL) cleaves citrate into acetyl-CoA and oxaloacetate in the cytoplasm, serving as the primary source of cytosolic acetyl-CoA. Cytosolic acetyl-CoA is the obligate substrate for histone acetyltransferases, directly linking nutrient/metabolic status to epigenetic regulation of gene expression. Adequate ATPCL activity supports histone acetylation homeostasis, which is critical for maintaining youthful transcriptional programs and chromatin accessibility. Loss of cytosolic acetyl-CoA supply leads to hypoacetylation of histones, a hallmark of epigenetic drift associated with aging. Additionally, acetyl-CoA produced by ATPCL feeds into lipid biosynthesis and protein acetylation, supporting broader anabolic and proteostatic functions that favor organismal health and longevity.",
"confidence": 0.62,
"key_pathways": [
"cytosolic acetyl-CoA production",
"histone acetylation / epigenetic regulation",
"lipid biosynthesis"
],
"mechanism_class": "epigenetic_alterations",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning about ATPCL's biochemical role (cytosolic acetyl-CoA production via citrate cleavage) is mechanistically accurate, but the model incorrectly assumed that this activity promotes longevity. In reality, ATPCL is anti-longevity in Drosophila, meaning its activity shortens lifespan (or its reduction extends lifespan). The model's logic that \"adequate ATPCL activity supports histone acetylation homeostasis\" and thus promotes longevity is flawed in the context of this organism's aging biology. The model also incorrectly classified the mechanism as \"epigenetic_alterations\" when the anti-longevity effect likely involves metabolic dysregulation (e.g., excessive lipid synthesis, altered nutrient sensing). The model had moderate confidence (0.62) but was wrong on both the direction and the mechanistic framing.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}