MDH1
S. cerevisiae
malate dehydrogenase MDH1
What the model saw
Gene: MDH1 Organism: Saccharomyces cerevisiae Known functions: malate dehydrogenase MDH1. L-malate dehydrogenase (NAD+) activity. catalytic activity. mRNA binding. malate dehydrogenase activity. oxidoreductase activity. oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. protein binding.
View unredacted entry
malate dehydrogenase MDH1. L-malate dehydrogenase (NAD+) activity. catalytic activity. mRNA binding. malate dehydrogenase activity. oxidoreductase activity. oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor. protein binding.
Solver output
MDH1 encodes the mitochondrial malate dehydrogenase in S. cerevisiae, which catalyzes the NAD+-dependent interconversion of malate to oxaloacetate in the TCA cycle. This reaction is central to maintaining mitochondrial redox balance (NAD+/NADH ratio) and sustaining oxidative phosphorylation efficiency. Proper TCA cycle flux supported by MDH1 is essential for mitochondrial membrane potential and ATP production; loss of MDH1 impairs respiratory competence and accelerates the petite mutation rate in yeast, a hallmark of mitochondrial deterioration associated with aging. Additionally, the malate-aspartate shuttle, in which MDH1 participates, is critical for transferring reducing equivalents across the mitochondrial membrane, and its disruption leads to elevated ROS and mitochondrial dysfunction. Maintenance of robust mitochondrial function through MDH1 activity is therefore expected to oppose aging-associated mitochondrial decline and support 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 predicted pro_longevity for MDH1 in S. cerevisiae with good confidence (0.68). The mechanistic reasoning is sound and well-articulated: MDH1 encodes mitochondrial malate dehydrogenase, which is central to the TCA cycle, mitochondrial redox balance, and the malate-aspartate shuttle. The explanation that loss of MDH1 impairs respiratory competence and accelerates petite mutation rate is biologically plausible. The mechanism class "mitochondrial_dysfunction" is appropriate since MDH1 loss would cause mitochondrial dysfunction. The reasoning quality is high, though some specific claims (e.g., "accelerates the petite mutation rate") may be inferred rather than directly cited from literature. Overall, this is a well-reasoned correct prediction.
Raw API responses
solver
{
"reasoning": "MDH1 encodes the mitochondrial malate dehydrogenase in S. cerevisiae, which catalyzes the NAD+-dependent interconversion of malate to oxaloacetate in the TCA cycle. This reaction is central to maintaining mitochondrial redox balance (NAD+/NADH ratio) and sustaining oxidative phosphorylation efficiency. Proper TCA cycle flux supported by MDH1 is essential for mitochondrial membrane potential and ATP production; loss of MDH1 impairs respiratory competence and accelerates the petite mutation rate in yeast, a hallmark of mitochondrial deterioration associated with aging. Additionally, the malate-aspartate shuttle, in which MDH1 participates, is critical for transferring reducing equivalents across the mitochondrial membrane, and its disruption leads to elevated ROS and mitochondrial dysfunction. Maintenance of robust mitochondrial function through MDH1 activity is therefore expected to oppose aging-associated mitochondrial decline and support longevity.",
"confidence": 0.68,
"key_pathways": [
"TCA cycle / tricarboxylic acid cycle",
"mitochondrial NAD+/NADH redox balance",
"malate-aspartate shuttle"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for MDH1 in S. cerevisiae with good confidence (0.68). The mechanistic reasoning is sound and well-articulated: MDH1 encodes mitochondrial malate dehydrogenase, which is central to the TCA cycle, mitochondrial redox balance, and the malate-aspartate shuttle. The explanation that loss of MDH1 impairs respiratory competence and accelerates petite mutation rate is biologically plausible. The mechanism class \"mitochondrial_dysfunction\" is appropriate since MDH1 loss would cause mitochondrial dysfunction. The reasoning quality is high, though some specific claims (e.g., \"accelerates the petite mutation rate\") may be inferred rather than directly cited from literature. Overall, this is a well-reasoned correct prediction.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}