MRPL4
S. cerevisiae
mitochondrial 54S ribosomal protein uL29m MRPL4
What the model saw
Gene: MRPL4 Organism: Saccharomyces cerevisiae Known functions: mitochondrial 54S ribosomal protein uL29m MRPL4. protein binding. structural constituent of ribosome.
View unredacted entry
mitochondrial 54S ribosomal protein uL29m MRPL4. protein binding. structural constituent of ribosome.
Solver output
MRPL4 encodes the mitochondrial large ribosomal subunit protein uL29m, a structural constituent of the 54S mitoribosome in S. cerevisiae. Proper assembly and function of the mitoribosome is essential for translation of mitochondrially-encoded subunits of the oxidative phosphorylation complexes. Loss of mitoribosomal integrity leads to impaired OXPHOS, mitochondrial membrane potential collapse, and increased reactive oxygen species — hallmarks of mitochondrial dysfunction that accelerate aging. Maintenance of mitochondrial translation fidelity and respiratory competence is well-established as pro-longevity in yeast, where petite (respiration-deficient) mutants typically show reduced chronological and replicative lifespan under caloric restriction conditions. Thus, the normal function of MRPL4 in sustaining mitochondrial protein synthesis supports mitochondrial health and opposes aging-associated mitochondrial decline.
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 MRPL4 supports mitochondrial translation and OXPHOS, its loss would be harmful and thus its presence is pro-longevity. However, in yeast replicative lifespan studies, deletion of mitoribosomal genes like MRPL4 often extends lifespan — likely because loss of mitochondrial translation triggers retrograde signaling or reduces mitochondrial activity in ways that paradoxically promote longevity. This is a well-known phenomenon in yeast where many mitoribosomal protein deletions are anti-longevity (i.e., the gene's normal function shortens lifespan). The model's mechanistic reasoning was plausible on the surface but missed the key empirical finding that MRPL4 is anti-longevity (its presence shortens lifespan). The model was moderately confident (0.62) in the wrong direction.
Raw API responses
solver
{
"reasoning": "MRPL4 encodes the mitochondrial large ribosomal subunit protein uL29m, a structural constituent of the 54S mitoribosome in S. cerevisiae. Proper assembly and function of the mitoribosome is essential for translation of mitochondrially-encoded subunits of the oxidative phosphorylation complexes. Loss of mitoribosomal integrity leads to impaired OXPHOS, mitochondrial membrane potential collapse, and increased reactive oxygen species — hallmarks of mitochondrial dysfunction that accelerate aging. Maintenance of mitochondrial translation fidelity and respiratory competence is well-established as pro-longevity in yeast, where petite (respiration-deficient) mutants typically show reduced chronological and replicative lifespan under caloric restriction conditions. Thus, the normal function of MRPL4 in sustaining mitochondrial protein synthesis supports mitochondrial health and opposes aging-associated mitochondrial decline.",
"confidence": 0.62,
"key_pathways": [
"mitochondrial translation / 54S mitoribosome assembly",
"oxidative phosphorylation (OXPHOS)",
"mitochondrial membrane potential maintenance"
],
"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 MRPL4 supports mitochondrial translation and OXPHOS, its loss would be harmful and thus its presence is pro-longevity. However, in yeast replicative lifespan studies, deletion of mitoribosomal genes like MRPL4 often extends lifespan — likely because loss of mitochondrial translation triggers retrograde signaling or reduces mitochondrial activity in ways that paradoxically promote longevity. This is a well-known phenomenon in yeast where many mitoribosomal protein deletions are anti-longevity (i.e., the gene's normal function shortens lifespan). The model's mechanistic reasoning was plausible on the surface but missed the key empirical finding that MRPL4 is anti-longevity (its presence shortens lifespan). The model was moderately confident (0.62) in the wrong direction.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}