SDH5
S. cerevisiae
succinate dehydrogenase assembly factor SDH5
What the model saw
Gene: SDH5 Organism: Saccharomyces cerevisiae Known functions: succinate dehydrogenase assembly factor SDH5. protein binding.
View unredacted entry
succinate dehydrogenase assembly factor SDH5. protein binding.
Solver output
SDH5 is an assembly factor required for the proper biogenesis of succinate dehydrogenase (Complex II of the mitochondrial electron transport chain). Complex II couples the oxidation of succinate to fumarate in the TCA cycle with the reduction of ubiquinone in the respiratory chain. Loss of SDH5 impairs Complex II assembly, leading to mitochondrial dysfunction, reduced oxidative phosphorylation efficiency, and potential accumulation of succinate, which can drive reactive oxygen species (ROS) production and metabolic imbalance. Proper mitochondrial respiratory function is strongly associated with longevity in yeast and other model organisms, as it supports efficient energy metabolism and limits oxidative damage. Therefore, SDH5's role in maintaining Complex II integrity supports mitochondrial health and is expected to be pro-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 is logically coherent but leads to the wrong conclusion. The model assumed that because SDH5 supports Complex II assembly and mitochondrial function, it must be pro-longevity. However, in yeast, SDH5 (and succinate dehydrogenase activity) is actually anti-longevity — likely because active respiration and TCA cycle flux can promote aging through ROS production or other mechanisms. The model's mechanistic reasoning about SDH5's role in Complex II assembly is correct, but the inference about its longevity effect is wrong. In yeast chronological or replicative aging contexts, reduced mitochondrial respiration (e.g., via retrograde signaling or caloric restriction mimicry) can actually extend lifespan, which is the opposite of what the model assumed. The model was fairly confident (0.72) in its wrong answer.
Raw API responses
solver
{
"reasoning": "SDH5 is an assembly factor required for the proper biogenesis of succinate dehydrogenase (Complex II of the mitochondrial electron transport chain). Complex II couples the oxidation of succinate to fumarate in the TCA cycle with the reduction of ubiquinone in the respiratory chain. Loss of SDH5 impairs Complex II assembly, leading to mitochondrial dysfunction, reduced oxidative phosphorylation efficiency, and potential accumulation of succinate, which can drive reactive oxygen species (ROS) production and metabolic imbalance. Proper mitochondrial respiratory function is strongly associated with longevity in yeast and other model organisms, as it supports efficient energy metabolism and limits oxidative damage. Therefore, SDH5's role in maintaining Complex II integrity supports mitochondrial health and is expected to be pro-longevity.",
"confidence": 0.72,
"key_pathways": [
"mitochondrial electron transport chain (Complex II assembly)",
"TCA cycle / succinate oxidation",
"oxidative phosphorylation"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning is logically coherent but leads to the wrong conclusion. The model assumed that because SDH5 supports Complex II assembly and mitochondrial function, it must be pro-longevity. However, in yeast, SDH5 (and succinate dehydrogenase activity) is actually anti-longevity — likely because active respiration and TCA cycle flux can promote aging through ROS production or other mechanisms. The model's mechanistic reasoning about SDH5's role in Complex II assembly is correct, but the inference about its longevity effect is wrong. In yeast chronological or replicative aging contexts, reduced mitochondrial respiration (e.g., via retrograde signaling or caloric restriction mimicry) can actually extend lifespan, which is the opposite of what the model assumed. The model was fairly confident (0.72) in its wrong answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}