Mitochondria and ceramide: Intertwined roles in regulation of apoptosis

The role of mitochondria as crucial participants in the cell death program is now becoming established. A growing body of work has also implicated sphingolipids, particularly ceramide, in apoptosis; however, the exact mechanism of how ceramide regulates the apoptotic pathway and its relationship to the mitochondrial role are still unanswered. Recently, our group has identified a mitochondrial ceramidase and we have shown that ceramide generation especially in mitochondria is able to induce apoptosis. Other studies also report on direct effects of ceramide on mitochondrial function in vitro and in cells. Taken together, these studies suggest an intimate interaction between ceramide and mitochondria in regulating apoptosis, including the existence of mitochondrial pathways of ceramide metabolism. This review summarizes the recent advances in the role of ceramide in cell death, mitochondrial function in apoptosis and the interactions of the two processes.