dnj-21
C. elegans
Mitochondrial import inner membrane translocase subunit TIM14
What the model saw
Gene: dnj-21 Organism: Caenorhabditis elegans Known functions: Mitochondrial import inner membrane translocase subunit TIM14. ATPase activator activity.
View unredacted entry
Mitochondrial import inner membrane translocase subunit TIM14. ATPase activator activity.
Solver output
dnj-21 encodes the C. elegans ortholog of TIM14 (DNAJC19/Pam18), a J-domain co-chaperone that is an essential component of the mitochondrial inner membrane translocase (TIM23) complex. Its ATPase activator activity stimulates the mtHsp70 (mortalin/GRP75) ATPase cycle, which drives the ATP-dependent import of nuclear-encoded preproteins across the inner mitochondrial membrane. Proper mitochondrial protein import is critical for maintaining mitochondrial proteostasis and respiratory chain assembly; loss of TIM14 function leads to impaired import, mitochondrial dysfunction, and proteotoxic stress. Functional TIM14 thus supports mitochondrial integrity and bioenergetic capacity, which are hallmarks of healthy aging in C. elegans. Additionally, mitochondrial import efficiency is linked to the mitochondrial unfolded protein response (UPRmt), a pathway known to promote longevity in C. elegans.
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 dnj-21. The mechanistic reasoning is well-grounded: dnj-21 encodes TIM14/DNAJC19, a J-domain co-chaperone in the TIM23 mitochondrial import complex that activates mtHsp70 ATPase activity. The model correctly connects mitochondrial protein import integrity to healthy aging and UPRmt in C. elegans. The reasoning is coherent and biologically accurate. Confidence of 0.72 is appropriate given the specificity of the gene. Minor note: the model's reasoning is somewhat inferential (functional TIM14 "supports" longevity) rather than citing direct experimental evidence of lifespan extension, but this is reasonable given the information provided.
Raw API responses
solver
{
"reasoning": "dnj-21 encodes the C. elegans ortholog of TIM14 (DNAJC19/Pam18), a J-domain co-chaperone that is an essential component of the mitochondrial inner membrane translocase (TIM23) complex. Its ATPase activator activity stimulates the mtHsp70 (mortalin/GRP75) ATPase cycle, which drives the ATP-dependent import of nuclear-encoded preproteins across the inner mitochondrial membrane. Proper mitochondrial protein import is critical for maintaining mitochondrial proteostasis and respiratory chain assembly; loss of TIM14 function leads to impaired import, mitochondrial dysfunction, and proteotoxic stress. Functional TIM14 thus supports mitochondrial integrity and bioenergetic capacity, which are hallmarks of healthy aging in C. elegans. Additionally, mitochondrial import efficiency is linked to the mitochondrial unfolded protein response (UPRmt), a pathway known to promote longevity in C. elegans.",
"confidence": 0.72,
"key_pathways": [
"TIM23 mitochondrial protein import complex",
"mtHsp70 ATPase chaperone cycle",
"mitochondrial unfolded protein response (UPRmt)"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly predicted pro_longevity for dnj-21. The mechanistic reasoning is well-grounded: dnj-21 encodes TIM14/DNAJC19, a J-domain co-chaperone in the TIM23 mitochondrial import complex that activates mtHsp70 ATPase activity. The model correctly connects mitochondrial protein import integrity to healthy aging and UPRmt in C. elegans. The reasoning is coherent and biologically accurate. Confidence of 0.72 is appropriate given the specificity of the gene. Minor note: the model's reasoning is somewhat inferential (functional TIM14 \"supports\" longevity) rather than citing direct experimental evidence of lifespan extension, but this is reasonable given the information provided.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}