TPO1
S. cerevisiae
polyamine transporter TPO1
What the model saw
Gene: TPO1 Organism: Saccharomyces cerevisiae Known functions: polyamine transporter TPO1. spermidine transmembrane transporter activity. spermine transmembrane transporter activity. transmembrane transporter activity.
View unredacted entry
polyamine transporter TPO1. spermidine transmembrane transporter activity. spermine transmembrane transporter activity. transmembrane transporter activity.
Solver output
TPO1 encodes a vacuolar/plasma membrane polyamine transporter in S. cerevisiae responsible for efflux of spermidine and spermine out of the cytoplasm. Intracellular polyamine homeostasis is tightly linked to longevity: spermidine in particular is a well-established pro-longevity molecule that induces autophagy via inhibition of EP300 acetyltransferase and promotes hypusination of eIF5A, both of which extend lifespan. TPO1-mediated export helps maintain cytoplasmic polyamine levels within an optimal range, preventing toxic accumulation while preserving the signaling pool. Proper polyamine trafficking intersects with the TOR nutrient-sensing pathway, as TOR regulates polyamine biosynthesis and autophagy induction. Loss of TPO1 leads to polyamine imbalance and sensitivity to polyamine stress, suggesting its normal function supports cellular homeostasis and stress resistance that underpin 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 predicts TPO1 as pro_longevity, matching the ground truth. However, the mechanistic reasoning is questionable. TPO1 is a polyamine transporter that exports spermidine/spermine, but the model's logic is somewhat contradictory: it argues that TPO1 exports polyamines to prevent toxic accumulation while also claiming spermidine is pro-longevity. If spermidine is pro-longevity and TPO1 exports it out of the cytoplasm, then TPO1 would reduce intracellular spermidine levels, which would seem anti-longevity by the model's own logic. The model tries to reconcile this by saying TPO1 maintains an "optimal range," but this is hand-wavy. The actual mechanism likely involves TPO1 preventing polyamine toxicity or maintaining compartment-specific polyamine levels rather than the autophagy/TOR pathway described. The mechanism_class of "deregulated_nutrient_sensing" is also a poor fit for a polyamine transporter. The reasoning contains internal inconsistencies and the mechanistic classification is not well-supported.
Raw API responses
solver
{
"reasoning": "TPO1 encodes a vacuolar/plasma membrane polyamine transporter in S. cerevisiae responsible for efflux of spermidine and spermine out of the cytoplasm. Intracellular polyamine homeostasis is tightly linked to longevity: spermidine in particular is a well-established pro-longevity molecule that induces autophagy via inhibition of EP300 acetyltransferase and promotes hypusination of eIF5A, both of which extend lifespan. TPO1-mediated export helps maintain cytoplasmic polyamine levels within an optimal range, preventing toxic accumulation while preserving the signaling pool. Proper polyamine trafficking intersects with the TOR nutrient-sensing pathway, as TOR regulates polyamine biosynthesis and autophagy induction. Loss of TPO1 leads to polyamine imbalance and sensitivity to polyamine stress, suggesting its normal function supports cellular homeostasis and stress resistance that underpin longevity.",
"confidence": 0.72,
"key_pathways": [
"spermidine/spermine homeostasis",
"autophagy induction via polyamine signaling",
"TOR nutrient-sensing pathway"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicts TPO1 as pro_longevity, matching the ground truth. However, the mechanistic reasoning is questionable. TPO1 is a polyamine transporter that exports spermidine/spermine, but the model's logic is somewhat contradictory: it argues that TPO1 exports polyamines to prevent toxic accumulation while also claiming spermidine is pro-longevity. If spermidine is pro-longevity and TPO1 exports it out of the cytoplasm, then TPO1 would reduce intracellular spermidine levels, which would seem anti-longevity by the model's own logic. The model tries to reconcile this by saying TPO1 maintains an \"optimal range,\" but this is hand-wavy. The actual mechanism likely involves TPO1 preventing polyamine toxicity or maintaining compartment-specific polyamine levels rather than the autophagy/TOR pathway described. The mechanism_class of \"deregulated_nutrient_sensing\" is also a poor fit for a polyamine transporter. The reasoning contains internal inconsistencies and the mechanistic classification is not well-supported.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": true,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}