mrpl-37
C. elegans
Large ribosomal subunit protein mL37
What the model saw
Gene: mrpl-37 Organism: Caenorhabditis elegans Known functions: Large ribosomal subunit protein mL37. structural constituent of ribosome.
View unredacted entry
Large ribosomal subunit protein mL37. structural constituent of ribosome.
Solver output
mrpl-37 encodes the mitochondrial large ribosomal subunit protein mL37, a structural component of the mitoribosome. Mitoribosomes are exclusively responsible for translating the 13 mitochondrially-encoded subunits of the oxidative phosphorylation complexes. Partial loss-of-function of mitoribosomal proteins in C. elegans has been shown to reduce mitochondrial translation and OXPHOS activity, which paradoxically activates the mitochondrial unfolded protein response (UPRmt) and can extend lifespan via retrograde signaling pathways involving ATFS-1. This mitohormesis mechanism — where mild mitochondrial stress promotes longevity — is well-documented for mitoribosomal subunit knockdowns in C. elegans. However, the normal (wild-type) function of mrpl-37 supports full mitochondrial translation capacity, which is required for organismal fitness; its loss, not its presence, tends to extend lifespan, suggesting the gene's normal function is modestly anti-longevity in the context of mitohormesis, but the pro-longevity framing applies if one considers that complete mitochondrial dysfunction is detrimental. Given the nuance, the balance of evidence in C. elegans RNAi screens places mitoribosomal subunit knockdown as lifespan-extending, implying the gene's normal function is mildly anti-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 identified the mechanistic pathway (mitoribosomal knockdown → UPRmt → lifespan extension via mitohormesis), which implies the gene's normal function is anti-longevity. However, the model's final prediction was "pro_longevity" despite its own reasoning explicitly concluding the gene's normal function is "mildly anti-longevity." The model contradicted itself: the reasoning correctly points to anti_longevity but the submitted answer was pro_longevity. This is a self-contradictory response where the correct conclusion was reached in the reasoning but the wrong label was output. The confidence of 0.62 also reflects the model's uncertainty. The mechanism described is largely correct (mitoribosomal subunit loss extends lifespan via UPRmt/mitohormesis), but the final answer label is wrong.
Raw API responses
solver
{
"reasoning": "mrpl-37 encodes the mitochondrial large ribosomal subunit protein mL37, a structural component of the mitoribosome. Mitoribosomes are exclusively responsible for translating the 13 mitochondrially-encoded subunits of the oxidative phosphorylation complexes. Partial loss-of-function of mitoribosomal proteins in C. elegans has been shown to reduce mitochondrial translation and OXPHOS activity, which paradoxically activates the mitochondrial unfolded protein response (UPRmt) and can extend lifespan via retrograde signaling pathways involving ATFS-1. This mitohormesis mechanism — where mild mitochondrial stress promotes longevity — is well-documented for mitoribosomal subunit knockdowns in C. elegans. However, the normal (wild-type) function of mrpl-37 supports full mitochondrial translation capacity, which is required for organismal fitness; its loss, not its presence, tends to extend lifespan, suggesting the gene's normal function is modestly anti-longevity in the context of mitohormesis, but the pro-longevity framing applies if one considers that complete mitochondrial dysfunction is detrimental. Given the nuance, the balance of evidence in C. elegans RNAi screens places mitoribosomal subunit knockdown as lifespan-extending, implying the gene's normal function is mildly anti-longevity.",
"confidence": 0.62,
"key_pathways": [
"mitochondrial translation / mitoribosome assembly",
"mitochondrial unfolded protein response (UPRmt / ATFS-1)",
"oxidative phosphorylation complex biogenesis"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identified the mechanistic pathway (mitoribosomal knockdown → UPRmt → lifespan extension via mitohormesis), which implies the gene's normal function is anti-longevity. However, the model's final prediction was \"pro_longevity\" despite its own reasoning explicitly concluding the gene's normal function is \"mildly anti-longevity.\" The model contradicted itself: the reasoning correctly points to anti_longevity but the submitted answer was pro_longevity. This is a self-contradictory response where the correct conclusion was reached in the reasoning but the wrong label was output. The confidence of 0.62 also reflects the model's uncertainty. The mechanism described is largely correct (mitoribosomal subunit loss extends lifespan via UPRmt/mitohormesis), but the final answer label is wrong.",
"failure_mode": "right_answer_wrong_reasoning",
"answer_correct": false,
"mechanism_correct": true,
"reasoning_quality": 3,
"ground_truth_questionable": false
}