mecr-1
C. elegans
Enoyl-
What the model saw
Gene: mecr-1 Organism: Caenorhabditis elegans Known functions: Enoyl-. enoyl-[acyl-carrier-protein] reductase (NADPH) activity. oxidoreductase activity.
View unredacted entry
Enoyl-. enoyl-[acyl-carrier-protein] reductase (NADPH) activity. oxidoreductase activity.
Solver output
mecr-1 encodes the mitochondrial enoyl-ACP reductase (MECR/ETR1), which catalyzes the final reductive step of mitochondrial fatty acid synthesis type II (mtFAS II), using NADPH to reduce enoyl-acyl carrier protein intermediates. mtFAS II is essential for the biosynthesis of lipoic acid and for the maturation of mitochondrial respiratory chain complexes, particularly complex I. Loss of mtFAS II function in model organisms leads to impaired mitochondrial respiration, reduced lipoylation of key metabolic enzymes (e.g., pyruvate dehydrogenase, α-ketoglutarate dehydrogenase), and mitochondrial dysfunction. Maintaining proper mitochondrial fatty acid synthesis and respiratory chain integrity is associated with healthy aging and longevity in C. elegans. Therefore, the normal function of mecr-1 supports mitochondrial health, placing it as a pro-longevity gene.
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 assumes that because mecr-1 supports mitochondrial health, it must be pro-longevity. However, in C. elegans, mitochondrial dysfunction (including impaired respiratory chain function) is actually well-known to extend lifespan through mechanisms like the mitochondrial unfolded protein response (UPRmt) and reduced insulin/IGF-1 signaling. The model failed to account for the paradoxical relationship between mitochondrial dysfunction and longevity in C. elegans, where loss-of-function of mitochondrial genes (including those in complex I) often extends lifespan. The mechanistic reasoning about mtFAS II and lipoic acid biosynthesis is biochemically accurate, but the conclusion drawn from it is incorrect in the context of C. elegans aging biology. The model's confidence of 0.62 is moderate but still wrong.
Raw API responses
solver
{
"reasoning": "mecr-1 encodes the mitochondrial enoyl-ACP reductase (MECR/ETR1), which catalyzes the final reductive step of mitochondrial fatty acid synthesis type II (mtFAS II), using NADPH to reduce enoyl-acyl carrier protein intermediates. mtFAS II is essential for the biosynthesis of lipoic acid and for the maturation of mitochondrial respiratory chain complexes, particularly complex I. Loss of mtFAS II function in model organisms leads to impaired mitochondrial respiration, reduced lipoylation of key metabolic enzymes (e.g., pyruvate dehydrogenase, α-ketoglutarate dehydrogenase), and mitochondrial dysfunction. Maintaining proper mitochondrial fatty acid synthesis and respiratory chain integrity is associated with healthy aging and longevity in C. elegans. Therefore, the normal function of mecr-1 supports mitochondrial health, placing it as a pro-longevity gene.",
"confidence": 0.62,
"key_pathways": [
"mitochondrial fatty acid synthesis type II (mtFAS II)",
"lipoic acid biosynthesis",
"mitochondrial respiratory chain complex assembly"
],
"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 assumes that because mecr-1 supports mitochondrial health, it must be pro-longevity. However, in C. elegans, mitochondrial dysfunction (including impaired respiratory chain function) is actually well-known to extend lifespan through mechanisms like the mitochondrial unfolded protein response (UPRmt) and reduced insulin/IGF-1 signaling. The model failed to account for the paradoxical relationship between mitochondrial dysfunction and longevity in C. elegans, where loss-of-function of mitochondrial genes (including those in complex I) often extends lifespan. The mechanistic reasoning about mtFAS II and lipoic acid biosynthesis is biochemically accurate, but the conclusion drawn from it is incorrect in the context of C. elegans aging biology. The model's confidence of 0.62 is moderate but still wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}