Essential Role of TID1 in Maintaining Mitochondrial Membrane Potential Homogeneity and Mitochondrial DNA Integrity
Bibliographic record
Abstract
The tumorous imaginal disc 1 (TID1) protein localizes mainly to the mitochondrial compartment, wherein its function remains largely unknown. Here we report that TID1 regulates the steady-state homogeneity of the mitochondrial membrane potential (Δψ) and maintains the integrity of mitochondrial DNA (mtDNA). Silencing of TID1 with RNA interference leads to changes in the distribution of Δψ along the mitochondrial network, characterized by an increase in Δψ in focal regions. This effect can be rescued by ectopic expression of a TID1 construct with an intact J domain. Chronic treatment with a low dose of oligomycin, an inhibitor of F1Fo ATP synthase, decreases the cellular ATP content and phenocopies TID1 loss of function, indicating a connection between the disruption of mitochondrial bioenergetics and hyperpolarization. Prolonged silencing of TID1 or low-dose oligomycin treatment leads to the loss of mtDNA and the consequent inhibition of oxygen consumption. Biochemical and colocalization data indicate that complex I aggregation underlies the focal accumulation of Δψ in TID1-silenced cells. Given that TID1 is proposed to function as a cochaperone, these data show that TID1 prevents complex I aggregation and support the existence of a TID1-mediated stress response to ATP synthase inhibition.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".