MRPL40
S. cerevisiae
mitochondrial 54S ribosomal protein uL24m MRPL40
What the model saw
Gene: MRPL40 Organism: Saccharomyces cerevisiae Known functions: mitochondrial 54S ribosomal protein uL24m MRPL40. protein binding. structural constituent of ribosome.
View unredacted entry
mitochondrial 54S ribosomal protein uL24m MRPL40. protein binding. structural constituent of ribosome.
Solver output
MRPL40 encodes the mitochondrial large ribosomal subunit protein uL24m, a structural constituent of the 54S mitoribosome in yeast. Proper assembly and function of the mitoribosome is essential for translation of mitochondrially-encoded oxidative phosphorylation (OXPHOS) subunits. Loss of mitoribosomal integrity impairs OXPHOS complex assembly, reduces mitochondrial membrane potential, and elevates reactive oxygen species — all hallmarks of mitochondrial dysfunction that accelerate aging. Functional MRPL40 thus supports mitochondrial respiratory capacity, which is broadly associated with healthy aging and longevity in yeast. Additionally, mitochondrial translation fidelity is linked to proteostasis within the organelle, further supporting a pro-longevity role for intact mitoribosome function.
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 assumed that because MRPL40 is a structural component of the mitoribosome, its loss would impair mitochondrial function and accelerate aging — therefore it must be pro_longevity. However, in yeast, deletion of many mitoribosomal genes actually extends lifespan, likely through retrograde signaling or mitohormesis mechanisms. The model failed to consider that loss of mitochondrial translation (and thus reduced OXPHOS) can paradoxically extend lifespan in yeast via reduced TOR signaling or other compensatory pathways. The anti_longevity classification means that MRPL40 deletion shortens lifespan, which is the opposite of what the model predicted. The mechanistic reasoning, while plausible on the surface, led to the wrong conclusion and didn't account for the complex relationship between mitochondrial function and yeast longevity.
Raw API responses
solver
{
"reasoning": "MRPL40 encodes the mitochondrial large ribosomal subunit protein uL24m, a structural constituent of the 54S mitoribosome in yeast. Proper assembly and function of the mitoribosome is essential for translation of mitochondrially-encoded oxidative phosphorylation (OXPHOS) subunits. Loss of mitoribosomal integrity impairs OXPHOS complex assembly, reduces mitochondrial membrane potential, and elevates reactive oxygen species — all hallmarks of mitochondrial dysfunction that accelerate aging. Functional MRPL40 thus supports mitochondrial respiratory capacity, which is broadly associated with healthy aging and longevity in yeast. Additionally, mitochondrial translation fidelity is linked to proteostasis within the organelle, further supporting a pro-longevity role for intact mitoribosome function.",
"confidence": 0.62,
"key_pathways": [
"mitochondrial translation / 54S mitoribosome assembly",
"oxidative phosphorylation (OXPHOS) complex biogenesis",
"mitochondrial proteostasis"
],
"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 assumed that because MRPL40 is a structural component of the mitoribosome, its loss would impair mitochondrial function and accelerate aging — therefore it must be pro_longevity. However, in yeast, deletion of many mitoribosomal genes actually extends lifespan, likely through retrograde signaling or mitohormesis mechanisms. The model failed to consider that loss of mitochondrial translation (and thus reduced OXPHOS) can paradoxically extend lifespan in yeast via reduced TOR signaling or other compensatory pathways. The anti_longevity classification means that MRPL40 deletion shortens lifespan, which is the opposite of what the model predicted. The mechanistic reasoning, while plausible on the surface, led to the wrong conclusion and didn't account for the complex relationship between mitochondrial function and yeast longevity.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}