miro-1
C. elegans
Mitochondrial Rho GTPase 1
What the model saw
Gene: miro-1 Organism: Caenorhabditis elegans Known functions: Mitochondrial Rho GTPase 1. GTP binding. GTPase activity. calcium ion binding.
View unredacted entry
Mitochondrial Rho GTPase 1. GTP binding. GTPase activity. calcium ion binding.
Solver output
MIRO-1 is a mitochondrial Rho GTPase that regulates mitochondrial trafficking and distribution along cytoskeletal tracks, using both GTP hydrolysis and calcium-sensing EF-hand domains. In C. elegans, miro-1 loss has been shown to impair mitochondrial transport and quality control, leading to accumulation of damaged mitochondria. The calcium-binding activity links mitochondrial positioning to local Ca2+ signals, which is critical for matching mitochondrial energy supply to cellular demand. Proper mitochondrial distribution and dynamics are essential for maintaining mitochondrial membrane potential and reducing ROS production, both of which are key determinants of lifespan in C. elegans. Loss of miro-1 disrupts mitochondrial network integrity and has been associated with reduced healthspan, placing its normal function in the pro-longevity category via maintenance of mitochondrial homeostasis.
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. This means miro-1 normally shortens lifespan (i.e., loss of miro-1 extends lifespan), which is the opposite of what the model concluded. The model reasoned that miro-1 loss impairs mitochondrial transport and quality control, leading to reduced healthspan — but the actual finding is that miro-1 loss extends lifespan, making it anti-longevity. The mechanistic reasoning about mitochondrial trafficking and calcium sensing is plausible in general terms, but the model drew the wrong directional conclusion about the longevity effect. Research has shown that miro-1 mutants in C. elegans actually live longer, possibly because reduced mitochondrial motility triggers mitophagy or stress responses that promote longevity. The model's confidence of 0.62 is moderate but still clearly wrong.
Raw API responses
solver
{
"reasoning": "MIRO-1 is a mitochondrial Rho GTPase that regulates mitochondrial trafficking and distribution along cytoskeletal tracks, using both GTP hydrolysis and calcium-sensing EF-hand domains. In C. elegans, miro-1 loss has been shown to impair mitochondrial transport and quality control, leading to accumulation of damaged mitochondria. The calcium-binding activity links mitochondrial positioning to local Ca2+ signals, which is critical for matching mitochondrial energy supply to cellular demand. Proper mitochondrial distribution and dynamics are essential for maintaining mitochondrial membrane potential and reducing ROS production, both of which are key determinants of lifespan in C. elegans. Loss of miro-1 disrupts mitochondrial network integrity and has been associated with reduced healthspan, placing its normal function in the pro-longevity category via maintenance of mitochondrial homeostasis.",
"confidence": 0.62,
"key_pathways": [
"mitochondrial trafficking and distribution",
"calcium-regulated mitochondrial dynamics",
"mitochondrial quality control"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model predicted pro_longevity but the ground truth is anti_longevity. This means miro-1 normally shortens lifespan (i.e., loss of miro-1 extends lifespan), which is the opposite of what the model concluded. The model reasoned that miro-1 loss impairs mitochondrial transport and quality control, leading to reduced healthspan — but the actual finding is that miro-1 loss extends lifespan, making it anti-longevity. The mechanistic reasoning about mitochondrial trafficking and calcium sensing is plausible in general terms, but the model drew the wrong directional conclusion about the longevity effect. Research has shown that miro-1 mutants in C. elegans actually live longer, possibly because reduced mitochondrial motility triggers mitophagy or stress responses that promote longevity. The model's confidence of 0.62 is moderate but still clearly wrong.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}