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NDE2

S. cerevisiae

NADH-ubiquinone reductase (H(+)-translocating) NDE2

What the model saw

Gene: NDE2
Organism: Saccharomyces cerevisiae
Known functions: NADH-ubiquinone reductase (H(+)-translocating) NDE2. NADH dehydrogenase (quinone) (non-electrogenic) activity. NADH dehydrogenase (ubiquinone) (non-electrogenic) activity. NADH dehydrogenase activity. oxidoreductase activity.
View unredacted entry
NADH-ubiquinone reductase (H(+)-translocating) NDE2. NADH dehydrogenase (quinone) (non-electrogenic) activity. NADH dehydrogenase (ubiquinone) (non-electrogenic) activity. NADH dehydrogenase activity. oxidoreductase activity.

Solver output

Predicted influence
Pro-longevity
Confidence
72%
Mechanism
Mitochondrial dysfunction
Reasoning

NDE2 encodes an external NADH dehydrogenase on the outer face of the inner mitochondrial membrane in S. cerevisiae. It oxidizes cytosolic NADH and feeds electrons into the ubiquinone pool of the mitochondrial electron transport chain, thereby maintaining cytosolic NAD+/NADH redox balance and supporting mitochondrial respiration. Proper NADH oxidation is critical for efficient oxidative phosphorylation and prevention of reductive stress; loss of NDE2 impairs mitochondrial respiratory capacity and cytosolic redox homeostasis. Maintaining robust mitochondrial electron transport chain function is a well-established pro-longevity mechanism in yeast, as mitochondrial dysfunction is a hallmark of aging. NDE2 (together with NDE1) is a key non-proton-pumping alternative NADH dehydrogenase that supports respiratory metabolism and caloric-restriction-like metabolic states associated with extended lifespan.

Key pathways
mitochondrial electron transport chain (NADH oxidation to ubiquinone)cytosolic NAD+/NADH redox homeostasisoxidative phosphorylation
Longevity influence
Pro-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
Correct
Mechanism
Correct
Reasoning quality
4/5
Failure mode
Correct
Notes

The model correctly predicted pro_longevity for NDE2 in S. cerevisiae. The mechanistic reasoning is sound and well-detailed: NDE2 is indeed an external NADH dehydrogenase that oxidizes cytosolic NADH, maintains NAD+/NADH redox balance, and supports mitochondrial respiration. The connection to pro-longevity through mitochondrial function and respiratory metabolism is appropriate. The model also correctly notes the relationship with NDE1 and caloric-restriction-like metabolic states. Confidence of 0.72 is reasonable. The reasoning is solid though slightly speculative in connecting to CR-like states without direct citation.

Raw API responses

solver

{
  "reasoning": "NDE2 encodes an external NADH dehydrogenase on the outer face of the inner mitochondrial membrane in S. cerevisiae. It oxidizes cytosolic NADH and feeds electrons into the ubiquinone pool of the mitochondrial electron transport chain, thereby maintaining cytosolic NAD+/NADH redox balance and supporting mitochondrial respiration. Proper NADH oxidation is critical for efficient oxidative phosphorylation and prevention of reductive stress; loss of NDE2 impairs mitochondrial respiratory capacity and cytosolic redox homeostasis. Maintaining robust mitochondrial electron transport chain function is a well-established pro-longevity mechanism in yeast, as mitochondrial dysfunction is a hallmark of aging. NDE2 (together with NDE1) is a key non-proton-pumping alternative NADH dehydrogenase that supports respiratory metabolism and caloric-restriction-like metabolic states associated with extended lifespan.",
  "confidence": 0.72,
  "key_pathways": [
    "mitochondrial electron transport chain (NADH oxidation to ubiquinone)",
    "cytosolic NAD+/NADH redox homeostasis",
    "oxidative phosphorylation"
  ],
  "mechanism_class": "mitochondrial_dysfunction",
  "longevity_influence": "pro_longevity"
}

advisor

{
  "notes": "The model correctly predicted pro_longevity for NDE2 in S. cerevisiae. The mechanistic reasoning is sound and well-detailed: NDE2 is indeed an external NADH dehydrogenase that oxidizes cytosolic NADH, maintains NAD+/NADH redox balance, and supports mitochondrial respiration. The connection to pro-longevity through mitochondrial function and respiratory metabolism is appropriate. The model also correctly notes the relationship with NDE1 and caloric-restriction-like metabolic states. Confidence of 0.72 is reasonable. The reasoning is solid though slightly speculative in connecting to CR-like states without direct citation.",
  "failure_mode": "correct",
  "answer_correct": true,
  "mechanism_correct": true,
  "reasoning_quality": 4,
  "ground_truth_questionable": false
}