ero-1
C. elegans
Endoplasmic oxidoreductin;Endoplasmic reticulum oxidoreductin-1
What the model saw
Gene: ero-1 Organism: Caenorhabditis elegans Known functions: Endoplasmic oxidoreductin;Endoplasmic reticulum oxidoreductin-1. FAD binding. flavin-dependent sulfhydryl oxidase activity. protein-disulfide reductase activity. thiol oxidase activity.
View unredacted entry
Endoplasmic oxidoreductin;Endoplasmic reticulum oxidoreductin-1. FAD binding. flavin-dependent sulfhydryl oxidase activity. protein-disulfide reductase activity. thiol oxidase activity.
Solver output
ERO-1 is the C. elegans ortholog of Ero1, an FAD-dependent sulfhydryl oxidase in the endoplasmic reticulum that drives oxidative protein folding by donating electrons from protein disulfide bonds to molecular oxygen via FAD, generating hydrogen peroxide as a byproduct. While ERO-1 is essential for disulfide bond formation and ER proteostasis, its activity is a major source of ER-localized reactive oxygen species (H2O2), which contributes to oxidative stress. In C. elegans, reduction of ero-1 function has been shown to extend lifespan, consistent with the idea that limiting ERO-1-driven oxidative burden in the ER is beneficial. The pro-aging effect operates through the PDI–ERO-1 oxidative folding relay: excessive ERO-1 activity overwhelms antioxidant defenses and promotes ER stress, linking it to both proteostasis disruption and oxidative damage rather than supporting longevity. Thus, the normal (wild-type) function of ero-1 is net anti-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 anti_longevity for ero-1 in C. elegans. The mechanistic reasoning is detailed and accurate: ERO-1 is an FAD-dependent sulfhydryl oxidase in the ER that drives oxidative protein folding via the PDI-ERO1 relay, generating H2O2 as a byproduct. The model correctly identifies that reduction of ero-1 function extends lifespan, making wild-type ero-1 anti-longevity. The mechanism class of "loss_of_proteostasis" is reasonable, though the oxidative stress angle is arguably the primary mechanism. The key pathways identified are all relevant and accurate. Confidence of 0.72 is appropriate given the specificity of the claim.
Raw API responses
solver
{
"reasoning": "ERO-1 is the C. elegans ortholog of Ero1, an FAD-dependent sulfhydryl oxidase in the endoplasmic reticulum that drives oxidative protein folding by donating electrons from protein disulfide bonds to molecular oxygen via FAD, generating hydrogen peroxide as a byproduct. While ERO-1 is essential for disulfide bond formation and ER proteostasis, its activity is a major source of ER-localized reactive oxygen species (H2O2), which contributes to oxidative stress. In C. elegans, reduction of ero-1 function has been shown to extend lifespan, consistent with the idea that limiting ERO-1-driven oxidative burden in the ER is beneficial. The pro-aging effect operates through the PDI–ERO-1 oxidative folding relay: excessive ERO-1 activity overwhelms antioxidant defenses and promotes ER stress, linking it to both proteostasis disruption and oxidative damage rather than supporting longevity. Thus, the normal (wild-type) function of ero-1 is net anti-longevity.",
"confidence": 0.72,
"key_pathways": [
"ER oxidative protein folding (PDI-ERO1 relay)",
"ROS generation via FAD-dependent thiol oxidase activity",
"ER proteostasis and unfolded protein response"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for ero-1 in C. elegans. The mechanistic reasoning is detailed and accurate: ERO-1 is an FAD-dependent sulfhydryl oxidase in the ER that drives oxidative protein folding via the PDI-ERO1 relay, generating H2O2 as a byproduct. The model correctly identifies that reduction of ero-1 function extends lifespan, making wild-type ero-1 anti-longevity. The mechanism class of \"loss_of_proteostasis\" is reasonable, though the oxidative stress angle is arguably the primary mechanism. The key pathways identified are all relevant and accurate. Confidence of 0.72 is appropriate given the specificity of the claim.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}