ucr-1
C. elegans
Cytochrome b-c1 complex subunit 1, mitochondrial;Peptidase M16 C-terminal domain-containing protein
What the model saw
Gene: ucr-1 Organism: Caenorhabditis elegans Known functions: Cytochrome b-c1 complex subunit 1, mitochondrial;Peptidase M16 C-terminal domain-containing protein. metal ion binding. metalloendopeptidase activity.
View unredacted entry
Cytochrome b-c1 complex subunit 1, mitochondrial;Peptidase M16 C-terminal domain-containing protein. metal ion binding. metalloendopeptidase activity.
Solver output
ucr-1 encodes the core subunit 1 (Rieske iron-sulfur protein scaffold/Core 1) of the mitochondrial cytochrome b-c1 complex (Complex III), which is essential for electron transfer from ubiquinol to cytochrome c in the mitochondrial respiratory chain. Proper Complex III function is required for efficient oxidative phosphorylation and maintenance of the mitochondrial membrane potential. In C. elegans, partial loss-of-function of electron transport chain components (e.g., isp-1, clk-1) can paradoxically extend lifespan via mitohormesis, but complete loss is lethal; however, the normal/wild-type function of ucr-1 supports mitochondrial integrity and ATP production, which is fundamentally pro-longevity. The metalloendopeptidase (Peptidase M16 C-terminal domain) activity may also contribute to mitochondrial protein quality control, further supporting proteostasis within the organelle. Loss of this subunit disrupts Complex III assembly and electron flow, leading to increased ROS leakage and mitochondrial dysfunction—hallmarks associated with accelerated aging. Therefore, the normal function of ucr-1 is pro-longevity by maintaining mitochondrial respiratory efficiency.
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 general logic that mitochondrial ETC components supporting oxidative phosphorylation are pro-longevity, but this is incorrect for ucr-1 in C. elegans. In C. elegans, many ETC components (including Complex III subunits) are actually anti-longevity — their knockdown/reduction extends lifespan via mitohormesis or reduced ROS production. The model acknowledged this paradox (citing isp-1, clk-1) but then dismissed it, concluding that the "normal function" of ucr-1 is pro-longevity. This reasoning is flawed: GenAge classifies genes based on experimental evidence of their effect on lifespan, and ucr-1 is anti_longevity, meaning its normal activity shortens lifespan (or its reduction extends it). The model's mechanistic reasoning about ROS and mitochondrial dysfunction leading to accelerated aging is the opposite of what is observed experimentally in C. elegans for this class of genes. The confidence of 0.72 is inappropriately high given the known complexity of ETC gene effects on C. elegans lifespan.
Raw API responses
solver
{
"reasoning": "ucr-1 encodes the core subunit 1 (Rieske iron-sulfur protein scaffold/Core 1) of the mitochondrial cytochrome b-c1 complex (Complex III), which is essential for electron transfer from ubiquinol to cytochrome c in the mitochondrial respiratory chain. Proper Complex III function is required for efficient oxidative phosphorylation and maintenance of the mitochondrial membrane potential. In C. elegans, partial loss-of-function of electron transport chain components (e.g., isp-1, clk-1) can paradoxically extend lifespan via mitohormesis, but complete loss is lethal; however, the normal/wild-type function of ucr-1 supports mitochondrial integrity and ATP production, which is fundamentally pro-longevity. The metalloendopeptidase (Peptidase M16 C-terminal domain) activity may also contribute to mitochondrial protein quality control, further supporting proteostasis within the organelle. Loss of this subunit disrupts Complex III assembly and electron flow, leading to increased ROS leakage and mitochondrial dysfunction—hallmarks associated with accelerated aging. Therefore, the normal function of ucr-1 is pro-longevity by maintaining mitochondrial respiratory efficiency.",
"confidence": 0.72,
"key_pathways": [
"mitochondrial electron transport chain (Complex III / cytochrome b-c1 complex)",
"oxidative phosphorylation",
"mitochondrial protein quality control"
],
"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 general logic that mitochondrial ETC components supporting oxidative phosphorylation are pro-longevity, but this is incorrect for ucr-1 in C. elegans. In C. elegans, many ETC components (including Complex III subunits) are actually anti-longevity — their knockdown/reduction extends lifespan via mitohormesis or reduced ROS production. The model acknowledged this paradox (citing isp-1, clk-1) but then dismissed it, concluding that the \"normal function\" of ucr-1 is pro-longevity. This reasoning is flawed: GenAge classifies genes based on experimental evidence of their effect on lifespan, and ucr-1 is anti_longevity, meaning its normal activity shortens lifespan (or its reduction extends it). The model's mechanistic reasoning about ROS and mitochondrial dysfunction leading to accelerated aging is the opposite of what is observed experimentally in C. elegans for this class of genes. The confidence of 0.72 is inappropriately high given the known complexity of ETC gene effects on C. elegans lifespan.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}