ArticleCell2012
Sphingolipid metabolism cooperates with BAK and BAX to promote the mitochondrial pathway of apoptosis.
Article in Cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 239 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
239 citing papers in PubMed.
- An enantioselective covalent inhibitor of BAX confers cytoprotection in vivo.Nature chemical biology · 2026Article
- Injectable microgels carrying engineered biomimetic nanoparticles for osteoarthritis therapy via dual-targeted senescent chondrocyte clearance and endogenous repair promotion.Bioactive materials · 2026Article
- BRD4-mediated ER membrane contact creates functionally distinct mitochondrial subtypes.Molecular cell · 2026Article
- Decoding the gut microbiota-mitochondrial-inflammasome axis in cardiovascular disease.Molecular and cellular biochemistry · 2026Review
- A gated hydrophobic funnel within BAX binds bioactive lipids to potentiate pro-apoptotic function.Nature communications · 2026Article
- The physiological and pathological effects of sphingolipid metabolism and signaling in the central nervous system.Brain pathology (Zurich, Switzerland) · 2026Review
- A novel prenylflavonoid with efficacy in cancer therapy by targeting ceramide-orchestrated signaling.Frontiers in pharmacology · 2026Article
- Stochasticity contributes to explaining minority and majority MOMP during apoptosis.Cell death & disease · 2025Article
- ASAH1-mediated sphingolipid metabolic reprogramming in venetoclax resistance of AML: beyond the monocytic phenotypes.BMC cancer · 2025Article
- Sphingosine 1-phosphate signalling in cancer stem cells.Oncogenesis · 2025Review
- Article
- UGT8 mediated sulfatide synthesis modulates BAX localization and dictates apoptosis sensitivity of colorectal cancer.Cell death and differentiation · 2025Article
- Combining Photodynamic Therapy and Targeted Drug Delivery Systems: Enhancing Mitochondrial Toxicity for Improved Cancer Outcomes.International journal of molecular sciences · 2024Review
- Dynamic death decisions: How mitochondrial dynamics shape cellular commitment to apoptosis and ferroptosis.Developmental cell · 2024Review
- Contribution of Keratinocytes in Skin Cancer Initiation and Progression.International journal of molecular sciences · 2024Review
- Covalent inhibition of pro-apoptotic BAX.Nature chemical biology · 2024Article
- Lipid unsaturation promotes BAX and BAK pore activity during apoptosis.Nature communications · 2024Article
- Directly targeting BAX for drug discovery: Therapeutic opportunities and challenges.Acta pharmaceutica Sinica. B · 2024Review
- Multiple molecular and cellular mechanisms of the antitumour effect of dihydromyricetin (Review).Biomedical reports · 2024Review
- Mitochondria-Modulating Liposomes Reverse Radio-Resistance for Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
179 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
8 authors.
Funding
Abstract
Mitochondria are functionally and physically associated with heterotypic membranes, yet little is known about how these interactions impact mitochondrial outer-membrane permeabilization (MOMP) and apoptosis. We observed that dissociation of heterotypic membranes from mitochondria inhibited BAK/BAX-dependent cytochrome c (cyto c) release. Biochemical purification of neutral sphingomyelinases that correlated with MOMP sensitization suggested that sphingolipid metabolism coordinates BAK/BAX activation. Using purified lipids and enzymes, sensitivity to MOMP was achieved by in vitro reconstitution of the sphingolipid metabolic pathway. Sphingolipid metabolism inhibitors blocked MOMP from heavy membrane preparations but failed to influence MOMP in the presence of sphingolipid-reconstituted, purified mitochondria. Furthermore, the sphingolipid products, sphingosine-1-PO(4) and hexadecenal, cooperated specifically with BAK and BAX, respectively. Sphingolipid metabolism was also required for cellular responses to apoptosis. Our studies suggest that BAK/BAX activation and apoptosis are coordinated through BH3-only proteins and a specific lipid milieu that is maintained by heterotypic membrane-mitochondrial interactions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.