<i>S-</i> acylation of PNPLA2/ATGL: a necessity for triacylglycerol lipolysis and lipophagy in hepatocytes
Bibliographic record
Abstract
The intricate balance between lipolysis and lipophagy in cellular lipid homeostasis has fascinated researchers for years. A growing body of evidence highlights the critical roles of PNPLA2/ATGL (patatin like phospholipase domain containing 2) in both lipolysis and lipophagy. Here, we discuss our recent study, which revealed that PNPLA2 must be S-acylated on Cys15 for its robust catalytic activity. Additionally, we discuss the results highlighting that genetic inactivation of the ZDHHC11 acyltransferase or expression of S-acylation deficient PNPLA2 mutants impairs not only lipolysis but also lipophagy. This finding suggests that the mere presence of PNPLA2 with its LC3-interacting region (LIR) motifs is insufficient to drive lipophagy without triacylglycerol breakdown. Our study provides insights into yet another mode of regulation of PNPLA2 activity with implications for understanding lipid droplet catabolism, lipophagy, and cellular energy homeostasis.
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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".