SLP-2 regulates T cell activation by optimizing cardiolipin compartmentalization in mitochondrial membranes and enhancing cellular respiration (178.7)
Bibliographic record
Abstract
Abstract Stomatin-like protein 2 (SLP-2) is a mitochondrial protein of the highly conserved Stomatin, Prohibitin, Flotillin, HflC/K superfamily. The function of SLP-2 has remained unclear but members of this superfamily have been linked to membrane organization. We have previously reported that SLP-2 partitions within glycolipid-enriched, detergent-insoluble microdomains, and its expression is up-regulated upon T cell activation. This correlates with increased mitochondrial biogenesis and function. Using human inducible over-expression/down-regulation systems and newly generated T cell-specific SLP-2 knockout mice, we now report that SLP-2 binds directly and selectively to cardiolipin (CL) and interacts with prohibitins. Overexpression of SLP-2 leads to increased recruitment of prohibitins to mitochondrial membranes. This translates into optimal assembly and function of complexes I and II+III of the respiratory chain. SLP-2 deficiency in T cells is associated with abnormal CL compartmentalization and decreased respiration, which correlates with a selective post-transcriptional defect in the production of IL-2 and defective T cell (mostly CD4+) responses. Therefore, we propose that SLP-2 functions as an organizer of cardiolipin-enriched domains in mitochondrial membranes. These domains are required for optimal respiration and metabolic capacity during T cell activation. Our work also reveals a novel post-transcriptional checkpoint for IL-2 production under metabolic control.
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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".