dld-1
C. elegans
Dihydrolipoyl dehydrogenase, mitochondrial
What the model saw
Gene: dld-1 Organism: Caenorhabditis elegans Known functions: Dihydrolipoyl dehydrogenase, mitochondrial. dihydrolipoyl dehydrogenase (NADH) activity. flavin adenine dinucleotide binding. oxidoreductase activity. oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor.
View unredacted entry
Dihydrolipoyl dehydrogenase, mitochondrial. dihydrolipoyl dehydrogenase (NADH) activity. flavin adenine dinucleotide binding. oxidoreductase activity. oxidoreductase activity, acting on a sulfur group of donors, NAD(P) as acceptor.
Solver output
dld-1 encodes the mitochondrial dihydrolipoyl dehydrogenase (E3 subunit), a FAD-dependent oxidoreductase that is a shared component of the pyruvate dehydrogenase complex (PDC), alpha-ketoglutarate dehydrogenase complex (KGDHC), and branched-chain alpha-keto acid dehydrogenase complex. These complexes are central to mitochondrial oxidative metabolism and NADH production, feeding electrons into the electron transport chain. Elevated activity of these complexes increases mitochondrial respiration and reactive oxygen species (ROS) generation, which accelerates oxidative damage and aging. In C. elegans, partial reduction of mitochondrial ETC and TCA cycle activity (as seen in isp-1, clk-1, or nuo- mutants) paradoxically extends lifespan via mitohormesis and reduced ROS flux. Thus, the normal pro-oxidative function of dld-1 in driving NADH production and mitochondrial respiration is expected to be anti-longevity, as its loss or reduction would mimic the beneficial mitochondrial attenuation seen in long-lived worm mutants.
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 anti_longevity for dld-1. The mechanistic reasoning is sound and well-articulated: dld-1 encodes the E3 subunit of key mitochondrial dehydrogenase complexes, and its normal function drives mitochondrial respiration and ROS production. The model correctly draws the parallel to other C. elegans mitochondrial mutants (isp-1, clk-1, nuo-) where reduced mitochondrial activity extends lifespan via mitohormesis. The reasoning that dld-1's pro-oxidative function makes it anti-longevity (i.e., its loss would be beneficial) is logically consistent with the GenAge classification. Confidence of 0.72 is appropriate given the indirect inference. Minor caveat: the model's reasoning is somewhat generic about mitochondrial ROS rather than citing specific dld-1 experimental data in C. elegans, but the overall mechanistic framework is correct.
Raw API responses
solver
{
"reasoning": "dld-1 encodes the mitochondrial dihydrolipoyl dehydrogenase (E3 subunit), a FAD-dependent oxidoreductase that is a shared component of the pyruvate dehydrogenase complex (PDC), alpha-ketoglutarate dehydrogenase complex (KGDHC), and branched-chain alpha-keto acid dehydrogenase complex. These complexes are central to mitochondrial oxidative metabolism and NADH production, feeding electrons into the electron transport chain. Elevated activity of these complexes increases mitochondrial respiration and reactive oxygen species (ROS) generation, which accelerates oxidative damage and aging. In C. elegans, partial reduction of mitochondrial ETC and TCA cycle activity (as seen in isp-1, clk-1, or nuo- mutants) paradoxically extends lifespan via mitohormesis and reduced ROS flux. Thus, the normal pro-oxidative function of dld-1 in driving NADH production and mitochondrial respiration is expected to be anti-longevity, as its loss or reduction would mimic the beneficial mitochondrial attenuation seen in long-lived worm mutants.",
"confidence": 0.72,
"key_pathways": [
"TCA cycle / alpha-keto acid dehydrogenase complexes",
"mitochondrial NADH production and electron transport chain",
"mitohormesis / ROS signaling"
],
"mechanism_class": "mitochondrial_dysfunction",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for dld-1. The mechanistic reasoning is sound and well-articulated: dld-1 encodes the E3 subunit of key mitochondrial dehydrogenase complexes, and its normal function drives mitochondrial respiration and ROS production. The model correctly draws the parallel to other C. elegans mitochondrial mutants (isp-1, clk-1, nuo-) where reduced mitochondrial activity extends lifespan via mitohormesis. The reasoning that dld-1's pro-oxidative function makes it anti-longevity (i.e., its loss would be beneficial) is logically consistent with the GenAge classification. Confidence of 0.72 is appropriate given the indirect inference. Minor caveat: the model's reasoning is somewhat generic about mitochondrial ROS rather than citing specific dld-1 experimental data in C. elegans, but the overall mechanistic framework is correct.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 4,
"ground_truth_questionable": false
}