MRPL33
S. cerevisiae
mitochondrial 54S ribosomal protein uL30m MRPL33
What the model saw
Gene: MRPL33 Organism: Saccharomyces cerevisiae Known functions: mitochondrial 54S ribosomal protein uL30m MRPL33. structural constituent of ribosome.
View unredacted entry
mitochondrial 54S ribosomal protein uL30m MRPL33. structural constituent of ribosome.
Solver output
MRPL33 encodes a structural component of the mitochondrial large (54S) ribosomal subunit (uL30m), which is essential for translation of the mitochondrially-encoded subunits of the oxidative phosphorylation complexes. Proper mitochondrial ribosome assembly and function is required for maintaining respiratory chain integrity and mitochondrial membrane potential. Loss of mitochondrial translation capacity leads to mitochondrial dysfunction, increased reactive oxygen species production, and impaired ATP synthesis — all hallmarks associated with accelerated aging. In yeast, functional mitochondria are critical for chronological and replicative lifespan, and mutations disrupting mitochondrial ribosome components typically shorten lifespan. Therefore, the normal function of MRPL33 in supporting mitochondrial protein synthesis 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 follows a plausible but incorrect logic: it assumed that because MRPL33 supports mitochondrial translation, its loss would be harmful and thus the gene is pro-longevity. However, in yeast, deletion of mitochondrial ribosomal protein genes (including MRPL33) can actually extend lifespan — likely through mechanisms such as mitochondrial hormesis, retrograde signaling, or reduced OXPHOS activity mimicking caloric restriction effects. This is a known phenomenon in yeast where disruption of mitochondrial translation can paradoxically extend lifespan. The model's reasoning was coherent but based on an oversimplified assumption that mitochondrial dysfunction always shortens lifespan, missing the nuanced reality that in yeast, reduced mitochondrial ribosome function can be anti-longevity (i.e., the gene promotes aging when present, or deletion extends life). The confidence of 0.62 was moderate but still wrong. The mechanism class of mitochondrial_dysfunction is partially relevant but the directionality was wrong.
Raw API responses
solver
{
"reasoning": "MRPL33 encodes a structural component of the mitochondrial large (54S) ribosomal subunit (uL30m), which is essential for translation of the mitochondrially-encoded subunits of the oxidative phosphorylation complexes. Proper mitochondrial ribosome assembly and function is required for maintaining respiratory chain integrity and mitochondrial membrane potential. Loss of mitochondrial translation capacity leads to mitochondrial dysfunction, increased reactive oxygen species production, and impaired ATP synthesis — all hallmarks associated with accelerated aging. In yeast, functional mitochondria are critical for chronological and replicative lifespan, and mutations disrupting mitochondrial ribosome components typically shorten lifespan. Therefore, the normal function of MRPL33 in supporting mitochondrial protein synthesis is expected to be pro-longevity.",
"confidence": 0.62,
"key_pathways": [
"mitochondrial translation",
"oxidative phosphorylation",
"mitochondrial ribosome 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 follows a plausible but incorrect logic: it assumed that because MRPL33 supports mitochondrial translation, its loss would be harmful and thus the gene is pro-longevity. However, in yeast, deletion of mitochondrial ribosomal protein genes (including MRPL33) can actually extend lifespan — likely through mechanisms such as mitochondrial hormesis, retrograde signaling, or reduced OXPHOS activity mimicking caloric restriction effects. This is a known phenomenon in yeast where disruption of mitochondrial translation can paradoxically extend lifespan. The model's reasoning was coherent but based on an oversimplified assumption that mitochondrial dysfunction always shortens lifespan, missing the nuanced reality that in yeast, reduced mitochondrial ribosome function can be anti-longevity (i.e., the gene promotes aging when present, or deletion extends life). The confidence of 0.62 was moderate but still wrong. The mechanism class of mitochondrial_dysfunction is partially relevant but the directionality was wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}