AAC3
S. cerevisiae
ADP/ATP carrier protein AAC3
What the model saw
Gene: AAC3 Organism: Saccharomyces cerevisiae Known functions: ADP/ATP carrier protein AAC3. ATP:ADP antiporter activity. identical protein binding.
View unredacted entry
ADP/ATP carrier protein AAC3. ATP:ADP antiporter activity. identical protein binding.
Solver output
AAC3 encodes an ADP/ATP carrier (adenine nucleotide translocator) in the inner mitochondrial membrane that exchanges cytosolic ADP for matrix ATP, directly coupling mitochondrial oxidative phosphorylation to cytosolic energy demands. In yeast, AAC3 is the minor, hypoxia-induced paralog of the ADP/ATP carrier family; unlike AAC2 (the major aerobic isoform), AAC3 is associated with less efficient mitochondrial coupling and is expressed under conditions that favor fermentative metabolism. Overactive or dysregulated ADP/ATP exchange can increase mitochondrial membrane proton leak and reactive oxygen species (ROS) production, contributing to oxidative damage. Studies in yeast and other organisms show that reducing mitochondrial ADP/ATP translocase activity (particularly the less-coupled isoforms) can extend chronological and replicative lifespan, suggesting that AAC3's normal function promotes mitochondrial inefficiency and ROS-mediated damage rather than supporting longevity. Additionally, AAC3's role in fermentative conditions aligns with a metabolic state (high glycolysis, low OXPHOS) that is generally associated with shortened lifespan in yeast.
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 AAC3 as anti_longevity with a reasonable confidence of 0.62. The mechanistic reasoning is sound: AAC3 is correctly identified as a minor, hypoxia-induced ADP/ATP carrier paralog in yeast, and the model correctly reasons that its activity promotes mitochondrial inefficiency and ROS production, contributing to aging. The reasoning about AAC3's association with fermentative metabolism and less efficient mitochondrial coupling is accurate. The model appropriately distinguishes AAC3 from AAC2 (the major aerobic isoform). The reasoning is well-constructed and biologically plausible, though some specific claims (e.g., "overactive or dysregulated ADP/ATP exchange can increase mitochondrial membrane proton leak") could be more precisely stated. Overall, this is a high-quality prediction with correct answer and largely correct mechanistic reasoning.
Raw API responses
solver
{
"reasoning": "AAC3 encodes an ADP/ATP carrier (adenine nucleotide translocator) in the inner mitochondrial membrane that exchanges cytosolic ADP for matrix ATP, directly coupling mitochondrial oxidative phosphorylation to cytosolic energy demands. In yeast, AAC3 is the minor, hypoxia-induced paralog of the ADP/ATP carrier family; unlike AAC2 (the major aerobic isoform), AAC3 is associated with less efficient mitochondrial coupling and is expressed under conditions that favor fermentative metabolism. Overactive or dysregulated ADP/ATP exchange can increase mitochondrial membrane proton leak and reactive oxygen species (ROS) production, contributing to oxidative damage. Studies in yeast and other organisms show that reducing mitochondrial ADP/ATP translocase activity (particularly the less-coupled isoforms) can extend chronological and replicative lifespan, suggesting that AAC3's normal function promotes mitochondrial inefficiency and ROS-mediated damage rather than supporting longevity. Additionally, AAC3's role in fermentative conditions aligns with a metabolic state (high glycolysis, low OXPHOS) that is generally associated with shortened lifespan in yeast.",
"confidence": 0.62,
"key_pathways": [
"mitochondrial ADP/ATP exchange (adenine nucleotide translocator)",
"oxidative phosphorylation coupling",
"mitochondrial ROS production"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted AAC3 as anti_longevity with a reasonable confidence of 0.62. The mechanistic reasoning is sound: AAC3 is correctly identified as a minor, hypoxia-induced ADP/ATP carrier paralog in yeast, and the model correctly reasons that its activity promotes mitochondrial inefficiency and ROS production, contributing to aging. The reasoning about AAC3's association with fermentative metabolism and less efficient mitochondrial coupling is accurate. The model appropriately distinguishes AAC3 from AAC2 (the major aerobic isoform). The reasoning is well-constructed and biologically plausible, though some specific claims (e.g., \"overactive or dysregulated ADP/ATP exchange can increase mitochondrial membrane proton leak\") could be more precisely stated. Overall, this is a high-quality prediction with correct answer and largely correct mechanistic reasoning.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}