BCL2L13 Influences Autophagy and Ceramide Metabolism without Affecting Temozolomide Resistance in Glioblastoma
Bibliographic record
Abstract
Abstract Temozolomide (TMZ) resistance in glioblastoma (GBM) arises through metabolic rewiring that links mitochondrial function, autophagy balance, and sphingolipid metabolism. TMZ resistant (R) U251 cells exhibited suppressed apoptosis and complete blockade of autophagy flux, evidenced by LC3II and p62 accumulation and insensitivity to Bafilomycin A1. BCL2L13, strongly upregulated in R cells, emerged as a dual regulator of mitophagy and ceramide metabolism. BCL2L13 knockdown (KD) produced opposite effects in TMZ sensitive (NR) and resistant cells: in NR cells, KD elevated LC3II, reduced respiratory reserve, and triggered compensatory lipid synthesis; in R cells, KD decreased LC3II without restoring flux or TMZ sensitivity. Lipidomic profiling revealed that BCL2L13 loss reactivated CerS6 in NR cells, increasing C16:0 and mid-chain ceramides, while relieving CerS2 inhibition in R cells, elevating very long chain (C22 to C24) and glycosylated ceramides. These distinct sphingolipid signatures were confirmed by PLS-DA and KEGG enrichment, which highlighted steroid hormone, arachidonic, and linoleic acid metabolism in NR KD cells versus neuroactive ligand-receptor and signaling pathways in R KD cells. Together, these findings position BCL2L13 as a molecular integrator of mitochondrial respiration, autophagy flux, and CerS-dependent lipid remodeling, unveiling a context-specific metabolic mechanism that supports GBM cell survival under chemotherapeutic stress.
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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 | 0.000 | 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) | 0.001 | 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 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".