Faculty Opinions recommendation of Bcl-2 proteins EGL-1 and CED-9 do not regulate mitochondrial fission or fusion in Caenorhabditis elegans.
Bibliographic record
Abstract
The Bcl-2 family proteins are critical apoptosis regulators that associate with mitochondria and control the activation of caspases.Recently, both mammalian and C. elegans Bcl-2 proteins have been implicated in controlling mitochondrial fusion and fission processes in both living and apoptotic cells.To better understand the potential roles of Bcl-2 family proteins in regulating mitochondrial dynamics, we carried out a detailed analysis of mitochondria in animals that either lose or have increased activity of egl-1 and ced-9, two Bcl-2 family genes that induce and inhibit apoptosis in C. elegans, respectively.Unexpectedly, we found that loss of egl-1 or ced-9, or overexpression of their gene products, had no apparent effect on mitochondrial connectivity or mitochondrial size.Moreover, loss of ced-9 did not affect the mitochondrial morphology observed in a drp-1 mutant, where mitochondrial fusion occurs but mitochondrial fission is defective, or in a fzo-1 mutant, where mitochondrial fission occurs but mitochondrial fusion is restricted, suggesting that ced-9 is not required for either the mitochondrial fission or fusion process in C. elegans.Taken together, our results argue against an evolutionarily conserved role for Bcl-2 proteins in regulating mitochondrial fission and fusion. RESULTS Mitochondrial morphogenesis is not affected in egl-1(lf) or ced-9(lf) mutantsRecently, the C. elegans pro-apoptotic BH3-only Bcl-2 protein EGL-1 has been implicated in promoting mitochondria fission during apoptosis [1].In addition, the C. elegans anti-apoptotic Bcl-2 protein CED-9 was shown to mediate mitochondria fission during apoptosis in one study [1] but was found to promote mitochondria fusion in healthy cells in another [2], calling into question of the exact physiological roles of C. elegans Bcl-2 family proteins in regulating mitochondria dynamics.To address the critical issue of whether Bcl-2 proteins regulate normal mitochondrial fission or fusion process in C. elegans, we carried out a comprehensive analysis of mitochondria morphology and structure in animals that either lose or have increased activity of egl-1 or ced-9.First, we visualized mitochondria in early C. elegans embryos that were
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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 | 0.001 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.003 | 0.004 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.022 | 0.012 |
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".