Grant: Discovery Grants Program - Individual
Lakehead University
$33,000.00
Mitochondrial production and function of hydrogen sulphide
EF 2010-11
Résumé
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.
Programme
Discovery Grants Program - Individual
Bénéficiaire
Emplacement
Ontario, Canada
Type de bénéficiaire
Academia
Type
Grant
Source
NSERC's Awards Data
Tel que publié
Application id
171409-2010
Name nom
Wang, Rui
Department département
Biology
Organization id
25
Institution établissement
Lakehead University
Province en
Ontario
Province fr
Ontario
Country en
CANADA
Country fr
CANADA
Fiscal year exercice financier
2010
Competition year année de concours
2010
Award amount
33000
Program id
RGPIN
Program name en
Discovery Grants Program - Individual
Program name fr
Programme de subventions à la découverte - individuelles
Group en
Discovery grants programs
Group fr
Programmes de subventions à la découverte
Committee code
1501
Committee name en
Genes, Cells and Molecules
Committee name fr
Gènes, cellules et molécules
Area of application code
1201
Area of application group en
Advancement of knowledge
Area of application group fr
Avancement des connaissances
Area of application en
Life sciences (including biotechnology)
Area of application fr
Sciences de la vie (y compris biotechnologie)
Research subject code
5305
Research subject group en
Molecular biology
Research subject group fr
Biologie moléculaire
Research subject en
Protein manipulation and expression
Research subject fr
Expression et recombinaison protéiques
Partie
1
Nb partie
1
Application title
Mitochondrial production and function of hydrogen sulphide
Keyword
NSERC
Application summary
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.
