YFH1
S. cerevisiae
ferroxidase
What the model saw
Gene: YFH1 Organism: Saccharomyces cerevisiae Known functions: ferroxidase. 2 iron, 2 sulfur cluster binding. ferric iron binding. ferrous iron binding. ferroxidase activity. identical protein binding. iron chaperone activity. protein binding.
View unredacted entry
ferroxidase. 2 iron, 2 sulfur cluster binding. ferric iron binding. ferrous iron binding. ferroxidase activity. identical protein binding. iron chaperone activity. protein binding.
Solver output
YFH1 (yeast frataxin homolog) is a mitochondrial iron chaperone that binds ferrous and ferric iron and exhibits ferroxidase activity, oxidizing Fe²⁺ to Fe³⁺ to safely sequester iron and facilitate iron-sulfur (Fe-S) cluster assembly. By preventing the accumulation of free labile iron in the mitochondrial matrix, YFH1 suppresses Fenton chemistry-driven hydroxyl radical production, thereby limiting oxidative damage to mitochondrial DNA, proteins, and lipids. Loss of YFH1 leads to mitochondrial iron overload, respiratory dysfunction, and elevated reactive oxygen species — a phenotype analogous to Friedreich's ataxia in humans. Maintaining mitochondrial iron homeostasis and Fe-S cluster biogenesis is essential for electron transport chain integrity and overall mitochondrial function, both of which are central determinants of yeast replicative and chronological lifespan. Thus, the normal function of YFH1 directly opposes mitochondrial dysfunction and oxidative stress, promoting 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 YFH1 as pro_longevity with high confidence (0.82). The mechanistic reasoning is excellent and accurate: YFH1 (yeast frataxin homolog) functions as a mitochondrial iron chaperone with ferroxidase activity, preventing free iron accumulation, suppressing Fenton chemistry-driven ROS production, and supporting Fe-S cluster assembly. The analogy to Friedreich's ataxia is appropriate. The model correctly identifies that loss of YFH1 leads to mitochondrial iron overload and oxidative stress, making it a pro-longevity gene. All key pathways identified are relevant and accurate.
Raw API responses
solver
{
"reasoning": "YFH1 (yeast frataxin homolog) is a mitochondrial iron chaperone that binds ferrous and ferric iron and exhibits ferroxidase activity, oxidizing Fe²⁺ to Fe³⁺ to safely sequester iron and facilitate iron-sulfur (Fe-S) cluster assembly. By preventing the accumulation of free labile iron in the mitochondrial matrix, YFH1 suppresses Fenton chemistry-driven hydroxyl radical production, thereby limiting oxidative damage to mitochondrial DNA, proteins, and lipids. Loss of YFH1 leads to mitochondrial iron overload, respiratory dysfunction, and elevated reactive oxygen species — a phenotype analogous to Friedreich's ataxia in humans. Maintaining mitochondrial iron homeostasis and Fe-S cluster biogenesis is essential for electron transport chain integrity and overall mitochondrial function, both of which are central determinants of yeast replicative and chronological lifespan. Thus, the normal function of YFH1 directly opposes mitochondrial dysfunction and oxidative stress, promoting longevity.",
"confidence": 0.82,
"key_pathways": [
"mitochondrial iron-sulfur cluster assembly",
"mitochondrial iron homeostasis / Fenton reaction suppression",
"reactive oxygen species detoxification"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identified YFH1 as pro_longevity with high confidence (0.82). The mechanistic reasoning is excellent and accurate: YFH1 (yeast frataxin homolog) functions as a mitochondrial iron chaperone with ferroxidase activity, preventing free iron accumulation, suppressing Fenton chemistry-driven ROS production, and supporting Fe-S cluster assembly. The analogy to Friedreich's ataxia is appropriate. The model correctly identifies that loss of YFH1 leads to mitochondrial iron overload and oxidative stress, making it a pro-longevity gene. All key pathways identified are relevant and accurate.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}