fh
D. melanogaster
frataxin
What the model saw
Gene: fh Organism: Drosophila melanogaster Known functions: frataxin. 2 iron, 2 sulfur cluster binding. enzyme activator activity. ferric iron binding. ferrous iron binding. ferroxidase activity. iron chaperone activity.
View unredacted entry
frataxin. 2 iron, 2 sulfur cluster binding. enzyme activator activity. ferric iron binding. ferrous iron binding. ferroxidase activity. iron chaperone activity.
Solver output
Frataxin (fh) is a mitochondrial iron chaperone that donates iron for Fe-S cluster biogenesis and heme synthesis, and its ferroxidase activity prevents toxic free ferrous iron accumulation via Fenton chemistry. By facilitating proper Fe-S cluster assembly on respiratory chain complexes (e.g., Complex I, II, III) and aconitase, frataxin is essential for mitochondrial electron transport chain integrity and ATP production. Loss of frataxin in Drosophila leads to mitochondrial iron overload, elevated reactive oxygen species, impaired oxidative phosphorylation, and shortened lifespan—mirroring Friedreich's ataxia pathology. Its iron chaperone and ferroxidase activities thus directly suppress mitochondrial oxidative damage and maintain bioenergetic homeostasis, both of which are central to longevity. Therefore, the normal function of fh is pro-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 predicted pro_longevity for frataxin (fh) in Drosophila melanogaster. The mechanistic reasoning is thorough and accurate: frataxin functions as a mitochondrial iron chaperone for Fe-S cluster biogenesis, its ferroxidase activity prevents toxic free iron accumulation via Fenton chemistry, and loss of frataxin leads to mitochondrial iron overload, elevated ROS, impaired oxidative phosphorylation, and shortened lifespan. The connection to Friedreich's ataxia pathology is also correctly noted. The confidence level of 0.88 is appropriate given the well-established biology of frataxin.
Raw API responses
solver
{
"reasoning": "Frataxin (fh) is a mitochondrial iron chaperone that donates iron for Fe-S cluster biogenesis and heme synthesis, and its ferroxidase activity prevents toxic free ferrous iron accumulation via Fenton chemistry. By facilitating proper Fe-S cluster assembly on respiratory chain complexes (e.g., Complex I, II, III) and aconitase, frataxin is essential for mitochondrial electron transport chain integrity and ATP production. Loss of frataxin in Drosophila leads to mitochondrial iron overload, elevated reactive oxygen species, impaired oxidative phosphorylation, and shortened lifespan—mirroring Friedreich's ataxia pathology. Its iron chaperone and ferroxidase activities thus directly suppress mitochondrial oxidative damage and maintain bioenergetic homeostasis, both of which are central to longevity. Therefore, the normal function of fh is pro-longevity.",
"confidence": 0.88,
"key_pathways": [
"mitochondrial Fe-S cluster biogenesis",
"iron homeostasis and ferroxidase activity",
"mitochondrial electron transport chain maintenance"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for frataxin (fh) in Drosophila melanogaster. The mechanistic reasoning is thorough and accurate: frataxin functions as a mitochondrial iron chaperone for Fe-S cluster biogenesis, its ferroxidase activity prevents toxic free iron accumulation via Fenton chemistry, and loss of frataxin leads to mitochondrial iron overload, elevated ROS, impaired oxidative phosphorylation, and shortened lifespan. The connection to Friedreich's ataxia pathology is also correctly noted. The confidence level of 0.88 is appropriate given the well-established biology of frataxin.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}