Ucp2
M. musculus
uncoupling protein 2 (mitochondrial, proton carrier)
What the model saw
Gene: Ucp2 Organism: Mus musculus Known functions: uncoupling protein 2 (mitochondrial, proton carrier). dicarboxylate carrier UCP2. 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 homodimerization activity. proton transmembrane transporter activity. secondary active sulfate transmembrane transporter activity.
View unredacted entry
uncoupling protein 2 (mitochondrial, proton carrier). dicarboxylate carrier UCP2. 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 homodimerization activity. proton transmembrane transporter activity. secondary active sulfate transmembrane transporter activity.
Solver output
UCP2 is a mitochondrial inner membrane proton carrier that uncouples the electron transport chain from ATP synthesis by dissipating the proton gradient, thereby reducing mitochondrial membrane potential. This mild uncoupling activity decreases the efficiency of oxidative phosphorylation and attenuates mitochondrial reactive oxygen species (ROS) production, as a lower proton-motive force reduces electron leak to oxygen at complexes I and III. Reduced mitochondrial ROS generation limits oxidative damage to mtDNA, proteins, and lipids—a key driver of mitochondrial dysfunction and aging. Additionally, UCP2's metabolite carrier activity (shuttling aspartate, malate, oxaloacetate) modulates the malate-aspartate shuttle and metabolic substrate availability, influencing cellular redox balance. Evidence from mouse models shows that UCP2 overexpression is associated with reduced oxidative stress and extended healthspan, consistent with a pro-longevity role via mitochondrial ROS buffering.
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 Mus musculus. The mechanistic reasoning is sound and well-articulated: UCP2 reduces mitochondrial ROS production through mild uncoupling, thereby limiting oxidative damage and promoting longevity. The model also correctly notes UCP2's metabolite carrier functions. The confidence of 0.68 is reasonable. The reasoning about UCP2 overexpression reducing oxidative stress is consistent with published literature. Minor caveat: the model's claim about "extended healthspan" from UCP2 overexpression mouse models is somewhat imprecise (the evidence is more nuanced), but the overall mechanistic framework is correct.
Raw API responses
solver
{
"reasoning": "UCP2 is a mitochondrial inner membrane proton carrier that uncouples the electron transport chain from ATP synthesis by dissipating the proton gradient, thereby reducing mitochondrial membrane potential. This mild uncoupling activity decreases the efficiency of oxidative phosphorylation and attenuates mitochondrial reactive oxygen species (ROS) production, as a lower proton-motive force reduces electron leak to oxygen at complexes I and III. Reduced mitochondrial ROS generation limits oxidative damage to mtDNA, proteins, and lipids—a key driver of mitochondrial dysfunction and aging. Additionally, UCP2's metabolite carrier activity (shuttling aspartate, malate, oxaloacetate) modulates the malate-aspartate shuttle and metabolic substrate availability, influencing cellular redox balance. Evidence from mouse models shows that UCP2 overexpression is associated with reduced oxidative stress and extended healthspan, consistent with a pro-longevity role via mitochondrial ROS buffering.",
"confidence": 0.68,
"key_pathways": [
"mitochondrial uncoupling / ROS attenuation",
"oxidative phosphorylation regulation",
"malate-aspartate shuttle / mitochondrial metabolite transport"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for Ucp2 in Mus musculus. The mechanistic reasoning is sound and well-articulated: UCP2 reduces mitochondrial ROS production through mild uncoupling, thereby limiting oxidative damage and promoting longevity. The model also correctly notes UCP2's metabolite carrier functions. The confidence of 0.68 is reasonable. The reasoning about UCP2 overexpression reducing oxidative stress is consistent with published literature. Minor caveat: the model's claim about \"extended healthspan\" from UCP2 overexpression mouse models is somewhat imprecise (the evidence is more nuanced), but the overall mechanistic framework is correct.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}