tim18
S. pombe
TIM22 inner membrane protein import complex and succinate dehydrogenase (SDH) anchor subunit Tim18
What the model saw
Gene: tim18 Organism: Schizosaccharomyces pombe Known functions: TIM22 inner membrane protein import complex and succinate dehydrogenase (SDH) anchor subunit Tim18. heme binding. protein-membrane adaptor activity. ubiquinone binding.
View unredacted entry
TIM22 inner membrane protein import complex and succinate dehydrogenase (SDH) anchor subunit Tim18. heme binding. protein-membrane adaptor activity. ubiquinone binding.
Solver output
Tim18 is a structural component of the TIM22 inner membrane protein import complex, which is essential for inserting multi-pass inner membrane proteins (including metabolite carriers) into the mitochondrial inner membrane. Proper mitochondrial protein import is critical for maintaining mitochondrial function and biogenesis. Additionally, Tim18 serves as an SDH anchor subunit and binds both heme and ubiquinone, directly linking it to the electron transport chain (Complex II/succinate dehydrogenase) and mitochondrial respiratory function. Loss of Tim18 would impair both mitochondrial protein import and succinate-dependent electron flow through the respiratory chain, leading to mitochondrial dysfunction—a hallmark of aging. Its normal function therefore supports mitochondrial integrity and energy metabolism, promoting longevity.
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 predicted pro_longevity but the ground truth is anti_longevity. The model's reasoning assumed that because Tim18 supports mitochondrial function, its normal activity would promote longevity. However, in S. pombe, tim18 is classified as anti_longevity, meaning its activity shortens lifespan (or its deletion extends lifespan). The model's mechanistic reasoning is plausible on the surface but leads to the wrong conclusion. The model was fairly confident (0.72) in its incorrect prediction. The reasoning quality is low because it failed to consider that mitochondrial components involved in SDH/Complex II can sometimes be anti-longevity (e.g., through ROS production or other mechanisms), and it defaulted to a simplistic "supports mitochondrial function = pro-longevity" logic without considering alternative possibilities.
Raw API responses
solver
{
"reasoning": "Tim18 is a structural component of the TIM22 inner membrane protein import complex, which is essential for inserting multi-pass inner membrane proteins (including metabolite carriers) into the mitochondrial inner membrane. Proper mitochondrial protein import is critical for maintaining mitochondrial function and biogenesis. Additionally, Tim18 serves as an SDH anchor subunit and binds both heme and ubiquinone, directly linking it to the electron transport chain (Complex II/succinate dehydrogenase) and mitochondrial respiratory function. Loss of Tim18 would impair both mitochondrial protein import and succinate-dependent electron flow through the respiratory chain, leading to mitochondrial dysfunction—a hallmark of aging. Its normal function therefore supports mitochondrial integrity and energy metabolism, promoting longevity.",
"confidence": 0.72,
"key_pathways": [
"TIM22 mitochondrial inner membrane protein import complex",
"Succinate dehydrogenase (Complex II) / electron transport chain",
"Ubiquinone-mediated mitochondrial respiration"
],
"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 assumed that because Tim18 supports mitochondrial function, its normal activity would promote longevity. However, in S. pombe, tim18 is classified as anti_longevity, meaning its activity shortens lifespan (or its deletion extends lifespan). The model's mechanistic reasoning is plausible on the surface but leads to the wrong conclusion. The model was fairly confident (0.72) in its incorrect prediction. The reasoning quality is low because it failed to consider that mitochondrial components involved in SDH/Complex II can sometimes be anti-longevity (e.g., through ROS production or other mechanisms), and it defaulted to a simplistic \"supports mitochondrial function = pro-longevity\" logic without considering alternative possibilities.",
"failure_mode": "confident_wrong",
"answer_correct": false,
"mechanism_correct": false,
"reasoning_quality": 2,
"ground_truth_questionable": false
}