sco-1
C. elegans
Thioredoxin domain-containing protein
What the model saw
Gene: sco-1 Organism: Caenorhabditis elegans Known functions: Thioredoxin domain-containing protein. copper chaperone activity. copper ion binding.
View unredacted entry
Thioredoxin domain-containing protein. copper chaperone activity. copper ion binding.
Solver output
SCO-1 is a copper chaperone with a thioredoxin domain that delivers copper to cytochrome c oxidase (Complex IV) subunits in the mitochondrial inner membrane. In C. elegans, sco-1 is the ortholog of human SCO1/SCO2, which are essential for the assembly and metalation of the CuA site of COX2 in Complex IV. Proper Complex IV assembly is required for efficient mitochondrial electron transport and oxidative phosphorylation; loss of sco-1 function leads to Complex IV deficiency, impaired mitochondrial respiration, and elevated reactive oxygen species. Paradoxically, mild mitochondrial dysfunction in C. elegans (e.g., via isp-1 or clk-1 mutations) can extend lifespan through mitohormesis, but severe Complex IV loss is generally detrimental. However, the normal (wild-type) function of sco-1—ensuring proper copper delivery and Complex IV assembly—supports mitochondrial integrity and proteostasis, which is fundamentally pro-longevity. The thioredoxin domain also contributes redox regulation during copper transfer, further protecting against oxidative damage in the mitochondria.
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 about SCO-1's role as a copper chaperone for Complex IV assembly is mechanistically plausible in general terms, but it reaches the wrong conclusion. The model acknowledges that loss of sco-1 leads to Complex IV deficiency and impaired respiration, and even notes that mild mitochondrial dysfunction can extend lifespan via mitohormesis. However, it then incorrectly concludes that the wild-type function of sco-1 is pro_longevity. In C. elegans, sco-1 is actually anti_longevity, meaning its normal function promotes aging (or its loss extends lifespan). This is consistent with the mitohormesis framework the model itself mentions - reduced Complex IV activity through sco-1 loss could extend lifespan. The model contradicts its own reasoning by dismissing the mitohormesis angle and defaulting to the assumption that supporting mitochondrial integrity is pro-longevity. The confidence of 0.72 is notably high for an incorrect answer.
Raw API responses
solver
{
"reasoning": "SCO-1 is a copper chaperone with a thioredoxin domain that delivers copper to cytochrome c oxidase (Complex IV) subunits in the mitochondrial inner membrane. In C. elegans, sco-1 is the ortholog of human SCO1/SCO2, which are essential for the assembly and metalation of the CuA site of COX2 in Complex IV. Proper Complex IV assembly is required for efficient mitochondrial electron transport and oxidative phosphorylation; loss of sco-1 function leads to Complex IV deficiency, impaired mitochondrial respiration, and elevated reactive oxygen species. Paradoxically, mild mitochondrial dysfunction in C. elegans (e.g., via isp-1 or clk-1 mutations) can extend lifespan through mitohormesis, but severe Complex IV loss is generally detrimental. However, the normal (wild-type) function of sco-1—ensuring proper copper delivery and Complex IV assembly—supports mitochondrial integrity and proteostasis, which is fundamentally pro-longevity. The thioredoxin domain also contributes redox regulation during copper transfer, further protecting against oxidative damage in the mitochondria.",
"confidence": 0.72,
"key_pathways": [
"cytochrome c oxidase (Complex IV) assembly",
"mitochondrial copper homeostasis",
"mitochondrial electron transport chain"
],
"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 about SCO-1's role as a copper chaperone for Complex IV assembly is mechanistically plausible in general terms, but it reaches the wrong conclusion. The model acknowledges that loss of sco-1 leads to Complex IV deficiency and impaired respiration, and even notes that mild mitochondrial dysfunction can extend lifespan via mitohormesis. However, it then incorrectly concludes that the wild-type function of sco-1 is pro_longevity. In C. elegans, sco-1 is actually anti_longevity, meaning its normal function promotes aging (or its loss extends lifespan). This is consistent with the mitohormesis framework the model itself mentions - reduced Complex IV activity through sco-1 loss could extend lifespan. The model contradicts its own reasoning by dismissing the mitohormesis angle and defaulting to the assumption that supporting mitochondrial integrity is pro-longevity. The confidence of 0.72 is notably high for an incorrect answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}