RIP1
S. cerevisiae
ubiquinol--cytochrome-c reductase catalytic subunit RIP1
What the model saw
Gene: RIP1 Organism: Saccharomyces cerevisiae Known functions: ubiquinol--cytochrome-c reductase catalytic subunit RIP1. 2 iron, 2 sulfur cluster binding. oxidoreductase activity. quinol-cytochrome-c reductase activity.
View unredacted entry
ubiquinol--cytochrome-c reductase catalytic subunit RIP1. 2 iron, 2 sulfur cluster binding. oxidoreductase activity. quinol-cytochrome-c reductase activity.
Solver output
RIP1 encodes the Rieske iron-sulfur protein (2Fe-2S cluster-binding subunit) of Complex III (ubiquinol-cytochrome c reductase) in the mitochondrial electron transport chain. Its quinol-cytochrome-c reductase activity is essential for electron transfer from ubiquinol to cytochrome c, a core step in oxidative phosphorylation and mitochondrial ATP production. Functional Complex III is required for maintaining mitochondrial membrane potential and efficient respiration, both of which are critical for yeast chronological and replicative lifespan. Loss of RIP1 disrupts the ETC, impairs mitochondrial function, and can increase reactive oxygen species leakage, all hallmarks of mitochondrial dysfunction that shorten lifespan. Therefore, the normal function of RIP1 supports mitochondrial integrity and promotes 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 assumes that because RIP1 is essential for Complex III function and mitochondrial respiration, its normal function must promote longevity. However, in yeast, RIP1 (and Complex III activity more broadly) has been shown to have anti-longevity effects. Paradoxically, loss of Complex III function in yeast can extend lifespan through mechanisms such as retrograde signaling, reduced ROS production from the ETC, or metabolic reprogramming. The model's mechanistic reasoning is also incorrect — it assumes that disrupting ETC shortens lifespan, when in fact for this gene in yeast, the opposite is true. The model was fairly confident (0.72) in its wrong answer.
Raw API responses
solver
{
"reasoning": "RIP1 encodes the Rieske iron-sulfur protein (2Fe-2S cluster-binding subunit) of Complex III (ubiquinol-cytochrome c reductase) in the mitochondrial electron transport chain. Its quinol-cytochrome-c reductase activity is essential for electron transfer from ubiquinol to cytochrome c, a core step in oxidative phosphorylation and mitochondrial ATP production. Functional Complex III is required for maintaining mitochondrial membrane potential and efficient respiration, both of which are critical for yeast chronological and replicative lifespan. Loss of RIP1 disrupts the ETC, impairs mitochondrial function, and can increase reactive oxygen species leakage, all hallmarks of mitochondrial dysfunction that shorten lifespan. Therefore, the normal function of RIP1 supports mitochondrial integrity and promotes longevity.",
"confidence": 0.72,
"key_pathways": [
"mitochondrial electron transport chain (Complex III)",
"oxidative phosphorylation",
"ubiquinol-cytochrome c reductase activity"
],
"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 assumes that because RIP1 is essential for Complex III function and mitochondrial respiration, its normal function must promote longevity. However, in yeast, RIP1 (and Complex III activity more broadly) has been shown to have anti-longevity effects. Paradoxically, loss of Complex III function in yeast can extend lifespan through mechanisms such as retrograde signaling, reduced ROS production from the ETC, or metabolic reprogramming. The model's mechanistic reasoning is also incorrect — it assumes that disrupting ETC shortens lifespan, when in fact for this gene in yeast, the opposite is true. The model was fairly confident (0.72) in its wrong answer.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}