Ceramide and mitochondria in ischemia/reperfusion.
A hallmark of tissue injury in various models of ischemia/reperfusion (IR) is mitochondrial dysfunction and the release of mitochondrial proapoptotic proteins leading to cell death. Although IR-induced mitochondrial injury has been extensively studied and key mitochondrial functions affected by IR are chiefly characterized, the nature of the molecule that causes loss of mitochondrial integrity and function remains obscure. It has become increasingly clear that ceramide, a membrane sphingolipid and a key mediator of cell stress responses, could play a critical role in IR-induced mitochondrial damage. Emerging data point to excessive ceramide accumulation in tissue and, specifically, in mitochondria after IR. Exogenously added to isolated mitochondria, ceramide could mimic some of the mitochondrial dysfunctions occurring in IR. The recent identification and characterization of major enzymes in ceramide synthesis is expected to contribute to the understanding of molecular mechanisms of ceramide involvement in mitochondrial damage in IR. This review will examine the experimental evidence supporting the important role of ceramide in mitochondrial dysfunction in IR to highlight potential targets for pharmacological manipulation of ceramide levels.
Novgorodov
Sergei A
SA
Department of Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Gudz
Tatyana I
TI
D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D016923:Cell Death; D002518:Ceramides / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D015427:Reperfusion Injury / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism
D002518:Ceramides; D013109:Sphingomyelins; D013108:Sphingomyelin Phosphodiesterase