cox-6A
C. elegans
Cytochrome c oxidase subunit 6A, mitochondrial
What the model saw
Gene: cox-6A Organism: Caenorhabditis elegans Known functions: Cytochrome c oxidase subunit 6A, mitochondrial. enzyme regulator activity.
View unredacted entry
Cytochrome c oxidase subunit 6A, mitochondrial. enzyme regulator activity.
Solver output
COX-6A is a structural/regulatory subunit of cytochrome c oxidase (Complex IV), the terminal electron acceptor of the mitochondrial electron transport chain (ETC). In C. elegans, the relationship between ETC function and longevity is paradoxical: full ETC activity supports normal metabolism, but partial reduction of ETC complex activity (e.g., via RNAi knockdown of various ETC subunits) is well-documented to extend lifespan through mechanisms involving reduced ROS production, activation of mitochondrial unfolded protein response (UPRmt), and altered NAD+/NADH ratios. Subunit 6A specifically has a regulatory role modulating Complex IV activity, meaning its loss could either impair oxidative phosphorylation sufficiently to trigger pro-longevity mitohormesis, or could cause detrimental mitochondrial dysfunction. Because both outcomes are plausible and the net effect depends on the degree of Complex IV impairment, the longevity influence is genuinely unclear without direct experimental data on cox-6A loss-of-function in C. elegans.
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 "unclear" while the ground truth is "anti_longevity." The model's reasoning about the paradoxical relationship between ETC function and longevity in C. elegans is generally sound (many ETC subunit knockdowns do extend lifespan), but it failed to account for the fact that cox-6A is specifically classified as anti_longevity, meaning its loss or reduction actually shortens lifespan rather than extending it. The model's reasoning was too focused on the possibility of pro-longevity mitohormesis and didn't sufficiently weight the possibility that cox-6A loss causes detrimental mitochondrial dysfunction. The mechanism class of "mitochondrial_dysfunction" is partially correct in that it involves mitochondria, but the directionality is wrong. The model's uncertainty was somewhat appropriate given the paradoxical nature of ETC-longevity relationships, but it should have leaned more toward anti_longevity given that cox-6A is a regulatory subunit whose loss could impair Complex IV function detrimentally.
Raw API responses
solver
{
"reasoning": "COX-6A is a structural/regulatory subunit of cytochrome c oxidase (Complex IV), the terminal electron acceptor of the mitochondrial electron transport chain (ETC). In C. elegans, the relationship between ETC function and longevity is paradoxical: full ETC activity supports normal metabolism, but partial reduction of ETC complex activity (e.g., via RNAi knockdown of various ETC subunits) is well-documented to extend lifespan through mechanisms involving reduced ROS production, activation of mitochondrial unfolded protein response (UPRmt), and altered NAD+/NADH ratios. Subunit 6A specifically has a regulatory role modulating Complex IV activity, meaning its loss could either impair oxidative phosphorylation sufficiently to trigger pro-longevity mitohormesis, or could cause detrimental mitochondrial dysfunction. Because both outcomes are plausible and the net effect depends on the degree of Complex IV impairment, the longevity influence is genuinely unclear without direct experimental data on cox-6A loss-of-function in C. elegans.",
"confidence": 0.45,
"key_pathways": [
"mitochondrial electron transport chain (Complex IV)",
"mitochondrial unfolded protein response (UPRmt)",
"oxidative phosphorylation / mitohormesis"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "unclear"
}advisor
{
"notes": "The model predicted \"unclear\" while the ground truth is \"anti_longevity.\" The model's reasoning about the paradoxical relationship between ETC function and longevity in C. elegans is generally sound (many ETC subunit knockdowns do extend lifespan), but it failed to account for the fact that cox-6A is specifically classified as anti_longevity, meaning its loss or reduction actually shortens lifespan rather than extending it. The model's reasoning was too focused on the possibility of pro-longevity mitohormesis and didn't sufficiently weight the possibility that cox-6A loss causes detrimental mitochondrial dysfunction. The mechanism class of \"mitochondrial_dysfunction\" is partially correct in that it involves mitochondria, but the directionality is wrong. The model's uncertainty was somewhat appropriate given the paradoxical nature of ETC-longevity relationships, but it should have leaned more toward anti_longevity given that cox-6A is a regulatory subunit whose loss could impair Complex IV function detrimentally.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 3,
"ground_truth_questionable": false
}