ArticleCell death & disease2015
Cytochrome c oxidase deficiency accelerates mitochondrial apoptosis by activating ceramide synthase 6.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 64 citations in OpenAlex.
- Proteolytic activation of executioner caspase-3 and -7 regulates different physiological processes in mice.The EMBO journal · 2026Article
- Aptamer-functionalized apoptotic vesicles ameliorate osteoarthritis via resuming mitochondria OXPHOS of chondrocytes.Science advances · 2026Article
- Exploring Ceramide C16:0 as a Novel Biomarker and Therapeutic Target for Atherosclerosis.Journal of the American Heart Association · 2026Review
- Whole-Genome Data to Investigate Recent and Historical Dog Introgression Patterns in Italian Wolves.Ecology and evolution · 2025Article
- DeSUMOylation of RBMX regulates exosomal sorting of cargo to promote renal tubulointerstitial fibrosis in diabetic kidney disease.Journal of advanced research · 2025Article
- Causal relationship between mitochondrial-associated proteins and cerebral aneurysms: a Mendelian randomization study.Frontiers in neurology · 2024Article
- Endoplasmic reticulum stress and mitochondrial dysfunction during aging: Role of sphingolipids.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2023Article
- Proteomic analysis of holocarboxylase synthetase deficient-MDA-MB-231 breast cancer cells revealed the biochemical changes associated with cell death, impaired growth signaling, and metabolism.Frontiers in molecular biosciences · 2023Article
- Contribution of specific ceramides to obesity-associated metabolic diseases.Cellular and molecular life sciences : CMLS · 2022Review
- High-throughput metabolomics reveals dysregulation of hydrophobic metabolomes in cancer cell lines by Eleusine indica.Scientific reports · 2022Article
- Familial Intracranial Aneurysm Requires Not Only Whole-Exome Sequencing, But Also Mitochondrial DNA Sequencing.Korean journal of radiology · 2022Article
- Bioinspired nonheme iron complex that triggers mitochondrial apoptotic signalling pathway specifically for colorectal cancer cells.Chemical science · 2022Article
- Epigenetic analysis in placentas from sickle cell disease patients reveals a hypermethylation profile.PloS one · 2022Article
- Sphingosine-1-phosphate lyase (SGPL1) deficiency is associated with mitochondrial dysfunction.The Journal of steroid biochemistry and molecular biology · 2020Article
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- Bismuth Porphyrin Antagonizes Cisplatin-Induced Nephrotoxicity via Unexpected Metallothionein-Independent Mechanisms.iScience · 2020Article
- Article
- Ceramides Profile Identifies Patients with More Advanced Stages of Colorectal Cancer.Biomolecules · 2020Article
- Myocardium Metabolism in Physiological and Pathophysiological States: Implications of Epicardial Adipose Tissue and Potential Therapeutic Targets.International journal of molecular sciences · 2020Review
- In vitro and in vivo evaluation of the neuroprotective activity of Uncaria hirsuta Haviland.Journal of food and drug analysis · 2020Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although numerous pathogenic changes within the mitochondrial respiratory chain (RC) have been associated with an elevated occurrence of apoptosis within the affected tissues, the mechanistic insight into how mitochondrial dysfunction initiates apoptotic cell death is still unknown. In this study, we show that the specific alteration of the cytochrome c oxidase (COX), representing a common defect found in mitochondrial diseases, facilitates mitochondrial apoptosis in response to oxidative stress. Our data identified an increased ceramide synthase 6 (CerS6) activity as an important pro-apoptotic response to COX dysfunction induced either by chemical or genetic approaches. The elevated CerS6 activity resulted in accumulation of the pro-apoptotic C16 : 0 ceramide, which facilitates the mitochondrial apoptosis in response to oxidative stress. Accordingly, inhibition of CerS6 or its specific knockdown diminished the increased susceptibility of COX-deficient cells to oxidative stress. Our results provide new insights into how mitochondrial RC dysfunction mechanistically interferes with the apoptotic machinery. On the basis of its pivotal role in regulating cell death upon COX dysfunction, CerS6 might potentially represent a novel target for therapeutic intervention in mitochondrial diseases caused by COX dysfunction.
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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.