ArticleCancer research2025
Ceramide-Induced Metabolic Stress Depletes Fumarate and Drives Mitophagy to Mediate Tumor Suppression.
Article in Cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 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
8 citing papers in PubMed.
- Nanomaterial-driven spatiotemporal autophagy modulation: The dual-edged sword in precision cancer therapy.Acta pharmaceutica Sinica. B · 2026Review
- Sterol regulatory element‑binding proteins: Master regulators of lipid metabolic reprogramming in cancer and emerging therapeutic targets (Review).Oncology reports · 2026Review
- Mitophagy interacts with mitochondrial dynamics and biogenesis, acting as a double-edged sword in digestive cancer.iScience · 2026Review
- Depression-induced systemic C16-ceramide deficiency promotes OSCC via attenuation of mitochondrial apoptosis.Cellular and molecular life sciences : CMLS · 2026Article
- Review
- Mitophagy and Cellular Homeostasis in Kidney Diseases: Mechanisms and Potential Therapeutics.International journal of biological sciences · 2026Review
- Mitophagy-driven immune evasion in skin cancer: multidimensional regulatory networks and context-dependent therapeutic strategies-a narrative review.Frontiers in immunology · 2026Review
- Mitochondria as the central regulator of cell death in bronchopulmonary dysplasia.Frontiers in physiology · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors.
Funding
Abstract
Bioactive ceramide induces cell death in part by promoting mitophagy. C18-ceramide levels are commonly reduced in head and neck squamous cell carcinoma, which correlates with poor prognosis, suggesting the potential of harnessing ceramide for cancer treatment. In this study, we evaluated the ability of the ceramide analog D-erythro-14-(1-pyridinium)-N-octadecanoyl-sphingosine selenite (LCL768) to induce mitophagy and metabolic stress in head and neck squamous cell carcinoma. Mechanistically, LCL768 induced ceramide synthase 1 (CerS1)-mediated endogenous C18-ceramide accumulation in mitochondria to mediate mitophagy, which did not require the CerS1 transporter p17/PERMIT but was dependent on DRP1 activation via nitrosylation at C644. DRP1 facilitated the anchoring of the endoplasmic reticulum (ER) and mitochondrial membranes by promoting the association between phosphatidylethanolamine in the ER and cardiolipin in mitochondrial membranes. Mutations of Drp1 that prevented its binding to ER and mitochondrial membranes blocked CerS1/C18-ceramide mitochondrial accumulation, inhibiting LCL768-mediated mitophagy. In addition, LCL768-driven mitophagy altered mitochondrial metabolism, resulting in fumarate depletion and leading to tumor suppression in vivo. Exogenous fumarate supplementation prevented LCL768-mediated mitophagy, mitochondrial trafficking of CerS1, ER-mitochondrial tethering, and tumor suppression in mice. Fumarate metabolism was associated with PARKIN succination at a catalytic cysteine (Cys431), inhibiting its association with PINK1 and ubiquitin, thereby preventing mitophagy. LCL768-induced fumarate depletion attenuated PARKIN succination to promote PARKIN activation and mitophagy, indicating a feedforward mechanism that regulates mitophagy and fumarate metabolism through PARKIN succination. These data provide a mechanism whereby LCL768/CerS1-C18-ceramide-mediated mitophagy and tumor suppression are regulated by Drp1 nitrosylation, fumarate depletion, and PARKIN succination, providing a metabolic stress signature for lethal mitophagy. SIGNIFICANCE: The identification of a metabolic link between ceramide-induced mitophagy, fission, and fumarate depletion reveals an effective tumor suppressive strategy for head and neck squamous cell carcinoma.
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.