Bioenergetics of stomatin-like protein-2-deficient T cells reveal a regulatory role for this protein in immunometabolism (P1173)
Bibliographic record
Abstract
Abstract Stomatin-like protein (SLP)-2 is a mainly mitochondrial protein identified in proteome analysis of glycolipid-enriched membrane microdomains of mammalian cells, and modulates T cell activation. To study SLP-2 function we generated T cell-specific SLP-2 knockout (SLP-2 T-K/O) mice since conventional SLP-2 knockout mice were embryonic lethal at the pre-implantation stage. These mice showed reduced CD4+ T cell responses and decreased respiratory complex I and II+III activities. Our mechanistic studies suggest SLP-2 recruits prohibitins to cardiolipin (CL)-enriched domains in the mitochondrial inner membrane to form specialized CL-enriched membrane microdomains, required for optimal cellular respiration. We hypothesized SLP-2 functions in this manner to regulate the bioenergetics of T cells. Seahorse XF analysis revealed that although SLP-2 T-K/O cells showed unaltered total cellular and mitochondrial oxygen consumption rates (OCRs), they had significantly greater non-mitochondrial OCR, mitochondrial OCR uncoupled from ATP synthesis, and greater reliance on glycolysis (71% of mice). Surprisingly, SLP-2 T-K/O cells exhibited greater spare respiratory capacity, a phenomenon not due to differential sensitivities of cells to uncoupling agents. This new immunometabolic phenotype suggests SLP-2 may regulate assembly of functional respiratory supercomplexes. Bioenergetic and biochemical analyses of mitochondria are underway to establish the regulatory role of SLP-2 in T cell metabolism.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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".