spg-7

C. elegans

AFG3-like protein spg-7

What the model saw

Gene: spg-7
Organism: Caenorhabditis elegans
Known functions: AFG3-like protein spg-7. ATP binding. ATP hydrolysis activity. ATP-dependent peptidase activity. metalloendopeptidase activity. zinc ion binding.

View unredacted entry

AFG3-like protein spg-7. ATP binding. ATP hydrolysis activity. ATP-dependent peptidase activity. metalloendopeptidase activity. zinc ion binding.

Solver output

Predicted influence

Pro-longevity

Confidence

75%

Mechanism

Mitochondrial dysfunction

Reasoning

SPG-7 is the C. elegans ortholog of human AFG3L2/paraplegin, a conserved mitochondrial AAA+ metalloprotease (m-AAA protease) embedded in the inner mitochondrial membrane. Its ATP-dependent metalloendopeptidase activity (zinc ion binding, ATP hydrolysis) is responsible for quality control of inner mitochondrial membrane proteins, including degradation of misfolded or damaged respiratory chain subunits. By maintaining the integrity of the mitochondrial proteome and supporting proper assembly of the electron transport chain, SPG-7 directly opposes mitochondrial dysfunction—a core hallmark of aging. Loss of m-AAA protease function leads to mitochondrial protein aggregation, impaired OXPHOS, and accelerated aging phenotypes, while its normal activity sustains mitochondrial homeostasis and promotes longevity.

Key pathways

mitochondrial protein quality control (m-AAA protease)mitochondrial inner membrane proteostasiselectron transport chain assembly

Longevity influence

Anti-longevity

Lifespan effect

Increase

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

Answer

✗Incorrect

Mechanism

✗Incorrect

Reasoning quality

2/5

Failure mode

Confident wrong

Notes

The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumes that SPG-7 (m-AAA protease) promotes longevity by maintaining mitochondrial protein quality control. However, in C. elegans, spg-7 is actually anti-longevity — loss of spg-7 function activates the mitochondrial unfolded protein response (UPRmt) and extends lifespan. This is a well-known finding in the aging field: spg-7 RNAi/knockdown extends C. elegans lifespan by inducing mitochondrial stress signaling. The model's mechanistic reasoning is inverted — it assumes that maintaining mitochondrial homeostasis promotes longevity, but in this case, the mild mitochondrial stress caused by spg-7 loss is what extends lifespan. The model was confident (0.75) in the wrong direction.

Raw API responses

solver

{
  "reasoning": "SPG-7 is the C. elegans ortholog of human AFG3L2/paraplegin, a conserved mitochondrial AAA+ metalloprotease (m-AAA protease) embedded in the inner mitochondrial membrane. Its ATP-dependent metalloendopeptidase activity (zinc ion binding, ATP hydrolysis) is responsible for quality control of inner mitochondrial membrane proteins, including degradation of misfolded or damaged respiratory chain subunits. By maintaining the integrity of the mitochondrial proteome and supporting proper assembly of the electron transport chain, SPG-7 directly opposes mitochondrial dysfunction—a core hallmark of aging. Loss of m-AAA protease function leads to mitochondrial protein aggregation, impaired OXPHOS, and accelerated aging phenotypes, while its normal activity sustains mitochondrial homeostasis and promotes longevity.",
  "confidence": 0.75,
  "key_pathways": [
    "mitochondrial protein quality control (m-AAA protease)",
    "mitochondrial inner membrane proteostasis",
    "electron transport chain assembly"
  ],
  "mechanism_class": "mitochondrial_dysfunction",
  "longevity_influence": "pro_longevity"
}

advisor

{
  "notes": "The model predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumes that SPG-7 (m-AAA protease) promotes longevity by maintaining mitochondrial protein quality control. However, in C. elegans, spg-7 is actually anti-longevity — loss of spg-7 function activates the mitochondrial unfolded protein response (UPRmt) and extends lifespan. This is a well-known finding in the aging field: spg-7 RNAi/knockdown extends C. elegans lifespan by inducing mitochondrial stress signaling. The model's mechanistic reasoning is inverted — it assumes that maintaining mitochondrial homeostasis promotes longevity, but in this case, the mild mitochondrial stress caused by spg-7 loss is what extends lifespan. The model was confident (0.75) in the wrong direction.",
  "failure_mode": "confident_wrong",
  "answer_correct": false,
  "mechanism_correct": false,
  "reasoning_quality": 2,
  "ground_truth_questionable": false
}