ucp2
D. melanogaster
uncoupling protein 2
What the model saw
Gene: UCP2 Organism: Drosophila melanogaster Known functions: uncoupling protein 2. dicarboxylate carrier SLC25A8. GDP binding. L-aspartate transmembrane transporter activity. antiporter activity. chloride transmembrane transporter activity. malate transmembrane transporter activity. oxaloacetate transmembrane transporter activity. oxidative phosphorylation uncoupler activity. phosphate ion uniporter activity. protein binding. protein homodimerization activity. proton transmembrane transporter activity. secondary active sulfate transmembrane transporter activity.
View unredacted entry
uncoupling protein 2. dicarboxylate carrier SLC25A8. GDP binding. L-aspartate transmembrane transporter activity. antiporter activity. chloride transmembrane transporter activity. malate transmembrane transporter activity. oxaloacetate transmembrane transporter activity. oxidative phosphorylation uncoupler activity. phosphate ion uniporter activity. protein binding. protein homodimerization activity. proton transmembrane transporter activity. secondary active sulfate transmembrane transporter activity.
Solver output
UCP2 is a mitochondrial inner membrane uncoupling protein that dissipates the proton gradient across the inner mitochondrial membrane, reducing the efficiency of oxidative phosphorylation. By uncoupling electron transport from ATP synthesis, UCP2 lowers the mitochondrial membrane potential, which attenuates the rate of superoxide and reactive oxygen species (ROS) production at complexes I and III. Reduced mitochondrial ROS generation decreases oxidative damage to macromolecules (proteins, lipids, DNA), a key driver of aging. This mild uncoupling mechanism is well-established as pro-longevity in multiple model organisms, including Drosophila, where reducing mitochondrial ROS extends lifespan. Additionally, UCP2's dicarboxylate/metabolite transport activity (malate, oxaloacetate, aspartate) may support metabolic flexibility and mitochondrial substrate shuttling, further buffering metabolic stress.
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 UCP2 in Drosophila melanogaster with high confidence (0.72). The mechanistic reasoning is excellent: it correctly identifies UCP2 as a mitochondrial uncoupling protein that reduces the proton gradient, lowers mitochondrial membrane potential, attenuates ROS production at complexes I and III, and thereby reduces oxidative damage — a well-established pro-longevity mechanism. The model also correctly notes the dicarboxylate transport functions listed in the entry. The reasoning is thorough, accurate, and well-supported by the literature.
Raw API responses
solver
{
"reasoning": "UCP2 is a mitochondrial inner membrane uncoupling protein that dissipates the proton gradient across the inner mitochondrial membrane, reducing the efficiency of oxidative phosphorylation. By uncoupling electron transport from ATP synthesis, UCP2 lowers the mitochondrial membrane potential, which attenuates the rate of superoxide and reactive oxygen species (ROS) production at complexes I and III. Reduced mitochondrial ROS generation decreases oxidative damage to macromolecules (proteins, lipids, DNA), a key driver of aging. This mild uncoupling mechanism is well-established as pro-longevity in multiple model organisms, including Drosophila, where reducing mitochondrial ROS extends lifespan. Additionally, UCP2's dicarboxylate/metabolite transport activity (malate, oxaloacetate, aspartate) may support metabolic flexibility and mitochondrial substrate shuttling, further buffering metabolic stress.",
"confidence": 0.72,
"key_pathways": [
"mitochondrial uncoupling / ROS attenuation",
"oxidative phosphorylation",
"mitochondrial metabolite transport (malate-aspartate shuttle)"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for UCP2 in Drosophila melanogaster with high confidence (0.72). The mechanistic reasoning is excellent: it correctly identifies UCP2 as a mitochondrial uncoupling protein that reduces the proton gradient, lowers mitochondrial membrane potential, attenuates ROS production at complexes I and III, and thereby reduces oxidative damage — a well-established pro-longevity mechanism. The model also correctly notes the dicarboxylate transport functions listed in the entry. The reasoning is thorough, accurate, and well-supported by the literature.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}