Reference number : GC-2017-Q1-01951, amendment number : , agreement type : G, recipient legal name : Wang, Rui (Laurentian University)|Wang, Rui (Université Laurentienne), recipient country : CA, recipient province : nan, recipient city : Ontario, recipient postal code : nan, program name english : Discovery Grants Program - Individual, program name french : Programme de subventions à la découverte - individuelles, program purpose english : Bioenergetics is the process whereby energy is generated from glycolysis in eukaryotes in the form of ATP. Anaerobic glycolysis occurs in the cytosol, which converts glucose to lactate while generating 2 ATP per glucose molecule. Aerobic glycolysis is completed in the mitochondrion, producing 30-32 ATP from each molecule of glucose via oxidative phosphorylation (OXPHOS). The regulation of bioenergetics depends on whether mitochondria are present, glucose and oxygen levels, and the effects of other endogenous regulators. 
 
Hydrogen sulfide (H 2 S) is one important endogenous factor. Its production and biological importance in eukaryotes have been known for more than a decade. The research supported by my previous NSERC Discovery grants has demonstrated, confirmed by numerous reports from other researchers, that H 2 S is generated in both the cytosol and mitochondrion in mammalian cells and that H 2 S regulates mitochondrial ATP production, promotes mitochondrial biogenesis, and affects cell viability. 
 
Mature mammalian red blood cells (RBCs) do not possess mitochondria and their bioenergetics relies on anaerobic glycolysis whereas avian RBCs have functional mitochondria and their bioenergetics involves both anaerobic glycolysis and OXPHOS. Whether mammalian and avian RBCs use the same or different mechanisms to produce H 2 S is unknown. The roles of H 2 S in the regulation of bioenergetics as well as viability of RBCs, in the presence or absence of mitochondria, have not been studied. 
 
We hypothesize that H 2 S differentially regulates anaerobic glycolysis and OXPHOS in mammalian and avian RBCs, exerting different functional impacts on the function and survival of these cells. The objectives of this program are to examine, in mitochondrion-free mouse RBCs and mitochondrion-containing chicken RBCs, 1) the production of endogenous H 2 S and its regulation; 2) the effects of H 2 S on anaerobic glycolysis and OXPHOS and the underlying mechanisms; 3) the impact of H 2 S-regulated bioenergetics on cellular survival and functions; and 4) the effects of polysulfide on bioenergetics and cell survival in comparison with those of H 2 S. These short-term objectives align with the long-term objective of my research career, i.e. to elucidate the metabolism and biological importance of gasotransmitters, including H 2 S, in eukaryotes. 
 
The proposed program can help better understand how the bioenergetics of RBCs is regulated by H 2 S to sustain the lifespan of these cells. New light will be shed on the significance of evolutionary extrusion of the mitochondrion from mammalian RBCs in connection to endogenous H 2 S metabolism. The knowledge gained will also help to devise H 2 S-based strategies to specifically regulate bioenergetics-dependent cellular and body functions, such as optimized storage conditions for RBCs in vitro , high altitude adaptation where oxygen supply is limited, or exercise and physical activities., program purpose french : Bioenergetics is the process whereby energy is generated from glycolysis in eukaryotes in the form of ATP. Anaerobic glycolysis occurs in the cytosol, which converts glucose to lactate while generating 2 ATP per glucose molecule. Aerobic glycolysis is completed in the mitochondrion, producing 30-32 ATP from each molecule of glucose via oxidative phosphorylation (OXPHOS). The regulation of bioenergetics depends on whether mitochondria are present, glucose and oxygen levels, and the effects of other endogenous regulators. 
 
Hydrogen sulfide (H 2 S) is one important endogenous factor. Its production and biological importance in eukaryotes have been known for more than a decade. The research supported by my previous NSERC Discovery grants has demonstrated, confirmed by numerous reports from other researchers, that H 2 S is generated in both the cytosol and mitochondrion in mammalian cells and that H 2 S regulates mitochondrial ATP production, promotes mitochondrial biogenesis, and affects cell viability. 
 
Mature mammalian red blood cells (RBCs) do not possess mitochondria and their bioenergetics relies on anaerobic glycolysis whereas avian RBCs have functional mitochondria and their bioenergetics involves both anaerobic glycolysis and OXPHOS. Whether mammalian and avian RBCs use the same or different mechanisms to produce H 2 S is unknown. The roles of H 2 S in the regulation of bioenergetics as well as viability of RBCs, in the presence or absence of mitochondria, have not been studied. 
 
We hypothesize that H 2 S differentially regulates anaerobic glycolysis and OXPHOS in mammalian and avian RBCs, exerting different functional impacts on the function and survival of these cells. The objectives of this program are to examine, in mitochondrion-free mouse RBCs and mitochondrion-containing chicken RBCs, 1) the production of endogenous H 2 S and its regulation; 2) the effects of H 2 S on anaerobic glycolysis and OXPHOS and the underlying mechanisms; 3) the impact of H 2 S-regulated bioenergetics on cellular survival and functions; and 4) the effects of polysulfide on bioenergetics and cell survival in comparison with those of H 2 S. These short-term objectives align with the long-term objective of my research career, i.e. to elucidate the metabolism and biological importance of gasotransmitters, including H 2 S, in eukaryotes. 
 
The proposed program can help better understand how the bioenergetics of RBCs is regulated by H 2 S to sustain the lifespan of these cells. New light will be shed on the significance of evolutionary extrusion of the mitochondrion from mammalian RBCs in connection to endogenous H 2 S metabolism. The knowledge gained will also help to devise H 2 S-based strategies to specifically regulate bioenergetics-dependent cellular and body functions, such as optimized storage conditions for RBCs in vitro , high altitude adaptation where oxygen supply is limited, or exercise and physical activities., agreement title english : Bioenergetics of red blood cells regulated by hydrogen sulfide, agreement title french : Bioenergetics of red blood cells regulated by hydrogen sulfide, agreement number : RGPIN, agreement value : 200000.0, agreement start date : 2017-05-10, agreement end date : nan, description english : nan, description french : nan, expected results english : nan, expected results french : nan, additional information english : Grant or Award spanning more than one fiscal year. (2017-2018 to 2022-2023), additional information french : Subvention ou bourse octroyée s'appliquant à plus d'un exercice financier. (2017-2018 à 2022-2023), owner organization : nserc-crsng, owner organization title : Natural Sciences and Engineering Research Council of Canada | Conseil de recherches en sciences naturelles et en génie du Canada