Mitochondrial production and function of hydrogen sulphide

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Being a double-membrane enclosed intracellular organelle, mitochondrion is the power house of eukaryotic cells where ATP is produced via oxidative phosphorylation. During the last NSERC-supported funding period, we have provided ample evidence for the physiological importance of hydrogen sulfide (H2S) for cellular metabolism and functions. This endogenous molecule of gas is produced from L-cysteine, catalyzed by an enzyme named cystathionine gamma-lyase (CSE). CSE usually is located in both the cytosol and mitochondria of the cells. We hypothesize that under various energy demanding conditions the allocation of CSE between the cytosol and mitochondria, i.e. redistribution, changes. This redistribution of CSE and its product H2S have the potential to affect the energy production and the survival of mammalian cells. This program will elucidate the functional consequence of this CSE redistribution inside the cells. Our objectives are to examine 1) mitochondrial CSE location and translocation and H2S production under different stress conditions, and 2) the role of H2S in regulation of mitochondrial structure and function as well as the underlying mechanisms. This research program is composed of 4 interlinked projects, conducted on cultured rat vascular smooth muscle cells. Project 1 will investigate the mitochondrial location of CSE and its redistribution under different energy demanding conditions. In Project 2, the question as to how this CSE mitochondrial translocation occurs will be addressed. The functional changes of mitochondria after this CSE redistribution will be the focus of Project 3. Finally, Project 4 will be devoted to the determination of the interaction of H2S with different structural components of mitochondria. This program may lead to a breakthrough in our understanding of fundamental sulfur metabolism in mammalian cells, of the evolution and etiology of mitochondria, and of the regulation of mitochondrial biogenesis and function in animal cardiovascular system as well as human's.