Plaat1 deficiency reduces cardiac cardiolipin content and impairs exercise tolerance
Bibliographic record
Abstract
Phospholipase A and acyltransferase 1 (PLAAT1) catalyzes O-transacylase, N-transacylase and phospholipase A 1/2 reactions. We have demonstrated that PLAAT1 has O-transacylase activity in vitro using phosphatidylcholine as an acyl donor, and monolysocardiolipin (MLCL) as an acyl acceptor, generating cardiolipin. However, a role for PLAAT1 in cardiolipin regulation in vivo has not yet been reported. We generated Plaat1 -deficient ( Plaat1 -/- ) mice and studied males and females for gross morphological differences, food intakes, respiratory gas exchange, total energy expenditure, and voluntary activity. We also evaluated cardiac cardiolipin contents, levels of mitochondrial proteins, and exercise capacity. Sex-matched Plaat1 -/- mice had highly similar body weights to their wildtype ( Wt ) littermates, although male Plaat1 -/- mice ate less. Male and female Plaat1 -/- hearts were 14.2% and 10.6% smaller, respectively. Cardiac cardiolipin levels were ∼1/3 lower in male and female Plaat1 -/- mice compared to their sex-matched Wt littermates, largely due to lower cardiolipin linoleate. Levels of the mitochondrial protein SDHA were 13.8% and 16.3% lower in male and female Plaat1 -/- mice, respectively. Both male and female Plaat1 -/- mice had significantly lower oxygen consumption, carbon dioxide production, and total energy expenditure, and male Plaat1 -/- mice had lower rearing activity than their sex-matched Wt littermates. While other measures of voluntary activity, including locomotion and ambulation did not differ significantly between genotypes, both males and females had reduced exercise tolerance. This work demonstrates a critical role for PLAAT1 in cardiac cardiolipin content and the regulation of energy metabolism and exercise tolerance in vivo .
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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 | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".