Ablation of ceramide synthase 2 causes chronic oxidative stress due to disruption of the mitochondrial respiratory chain

Hila Zigdon, Aviram Kogot-Levin, Joo Won Park, Ruth Goldschmidt, Samuel Kelly, Alfred H. Merrill, Avigdor Scherz, Yael Pewzner-Jung, Ann Saada, Anthony H. Futerman

Research output: Contribution to journalArticlepeer-review

128 Scopus citations

Abstract

Background: Ceramide synthase 2 null mice, which cannot synthesize very-long chain ceramides, display severe hepatopathy. Results: These mice have elevated sphinganine and altered N-acyl chain ceramides that disrupt mitochondrial function by modifying respiratory chain activity. Conclusion: Alteration of mitochondrial sphingolipids results in formation of reaction oxygen species in liver. Significance: Ceramides with defined acyl chains influence oxidative stress signaling pathways.

Original languageEnglish
Pages (from-to)4947-4956
Number of pages10
JournalJournal of Biological Chemistry
Volume288
Issue number7
DOIs
StatePublished - 15 Feb 2013

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