Investigating the Phosphorylation of C-Terminus of HSC70-Interacting Protein (CHIP) in Modulating PINK1/Parkin Mediated Mitochondrial Quality Control
Bibliographic record
Abstract
Mitochondrial dysfunction has been implicated in both sporadic and familial forms of Parkinson’s Disease (PD). Mutations in PINK1 and Parkin lead to early-onset autosomal recessive PD; these two proteins are known to be involved in maintaining mitochondrial quality control however it is unknown how their function is regulated. BAG5 is a co-chaperone protein known to impair Parkin’s E3 ubiquitin ligase function and its translocation to mitochondria and enhance neurodegeneration in models of PD. In a BAG5 interactome, the phosphorylation of the co-chaperone CHIP at serine 19 (S19) was upregulated upon mitochondrial dysfunction. We show that phosphorylation of CHIP is enhanced in the mitochondrial fraction only upon mitochondrial depolarization, and phosphorylation of CHIP modulates Parkin recruitment to mitochondria which may impact downstream mitochondrial clearance. p25 a known activator of kinases CDK5 and GSK-3β was identified to enhance CHIP phosphorylation. Understanding how mitochondrial quality control is modulated is essential to understanding PD.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| 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) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".