hsp-6
C. elegans
Heat shock protein hsp-6
What the model saw
Gene: hsp-6 Organism: Caenorhabditis elegans Known functions: Heat shock protein hsp-6. ATP binding. ATP hydrolysis activity. heat shock protein binding. protein folding chaperone. unfolded protein binding.
View unredacted entry
Heat shock protein hsp-6. ATP binding. ATP hydrolysis activity. heat shock protein binding. protein folding chaperone. unfolded protein binding.
Solver output
hsp-6 encodes the C. elegans mitochondrial HSP70 chaperone (mortalin/GRP75 ortholog), which is a core component of the mitochondrial unfolded protein response (UPRmt). Its ATP-dependent chaperone activity drives refolding of unfolded/misfolded proteins within the mitochondrial matrix, directly maintaining mitochondrial proteostasis. Activation of UPRmt via hsp-6 upregulation is well-established to extend lifespan in C. elegans, as demonstrated in studies involving mitochondrial stress (e.g., clk-1, isp-1 mutants) where hsp-6 induction is a key longevity signal. By binding unfolded proteins and coupling ATP hydrolysis to their refolding, hsp-6 prevents toxic protein aggregation in mitochondria, preserving organelle function and supporting longevity. Loss of hsp-6 function impairs UPRmt and reduces lifespan, confirming its pro-longevity role.
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 hsp-6 as pro_longevity with high confidence (0.82). The mechanistic reasoning is excellent: it correctly identifies hsp-6 as the C. elegans mitochondrial HSP70 chaperone (mortalin/GRP75 ortholog), correctly links it to the mitochondrial unfolded protein response (UPRmt), correctly notes that UPRmt activation extends lifespan in C. elegans, and correctly states that loss of hsp-6 impairs UPRmt and reduces lifespan. The key pathways identified are all accurate and relevant. The reasoning is detailed, accurate, and well-supported by the literature.
Raw API responses
solver
{
"reasoning": "hsp-6 encodes the C. elegans mitochondrial HSP70 chaperone (mortalin/GRP75 ortholog), which is a core component of the mitochondrial unfolded protein response (UPRmt). Its ATP-dependent chaperone activity drives refolding of unfolded/misfolded proteins within the mitochondrial matrix, directly maintaining mitochondrial proteostasis. Activation of UPRmt via hsp-6 upregulation is well-established to extend lifespan in C. elegans, as demonstrated in studies involving mitochondrial stress (e.g., clk-1, isp-1 mutants) where hsp-6 induction is a key longevity signal. By binding unfolded proteins and coupling ATP hydrolysis to their refolding, hsp-6 prevents toxic protein aggregation in mitochondria, preserving organelle function and supporting longevity. Loss of hsp-6 function impairs UPRmt and reduces lifespan, confirming its pro-longevity role.",
"confidence": 0.82,
"key_pathways": [
"mitochondrial unfolded protein response (UPRmt)",
"mitochondrial proteostasis/chaperone network",
"HSP70-mediated protein folding"
],
"mechanism_class": "loss_of_proteostasis",
"longevity_influence": "pro_longevity"
}advisor
{
"notes": "The model correctly identified hsp-6 as pro_longevity with high confidence (0.82). The mechanistic reasoning is excellent: it correctly identifies hsp-6 as the C. elegans mitochondrial HSP70 chaperone (mortalin/GRP75 ortholog), correctly links it to the mitochondrial unfolded protein response (UPRmt), correctly notes that UPRmt activation extends lifespan in C. elegans, and correctly states that loss of hsp-6 impairs UPRmt and reduces lifespan. The key pathways identified are all accurate and relevant. The reasoning is detailed, accurate, and well-supported by the literature.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}