Tuesday/Mardi, May/Mai 7
17:30-18:30
T. W. M Cameron Award/Prix
Outstanding PhD Thesis/Excellence de Thèse de PhD
Location/Lieu: Ballroom A and B
Chair/Animé par: Carol Bucking (York University, CSZ-SCZ president)
Hang Cheng, Faculty of Medicine, University of Ottawa
Hang Cheng gained extensive mitochondrial biology experience in the Pamenter Lab at the University of Ottawa where he completed his PhD. Following a year of postdoctoral training at Yale Med School studying the role of reactive oxygen species in epigenetic regulation, he returned to Ottawa to work with Stephen Ferguson on neurodegenerative disorders.
Chair/Animé par: Carol Bucking (York University, CSZ-SCZ president)
Hang Cheng, Faculty of Medicine, University of Ottawa
Hang Cheng gained extensive mitochondrial biology experience in the Pamenter Lab at the University of Ottawa where he completed his PhD. Following a year of postdoctoral training at Yale Med School studying the role of reactive oxygen species in epigenetic regulation, he returned to Ottawa to work with Stephen Ferguson on neurodegenerative disorders.
Mitochondria: Hubs of hypoxia-tolerance in naked mole-rats
Most adult mammals are highly sensitive to reduced oxygen availability; however, some species have evolved to live in hypoxic environments. Naked mole-rats (NMRs, Heterocephalus glaber) are among the most hypoxia-tolerant mammals and rapidly reduce whole animal oxygen consumption during hypoxia. Mitochondria are cellular oxygen sensors, major consumers of oxygen, and regulators of numerous cellular signalling pathways, and thus play key roles in cellular responses to hypoxia. However, little is known about the specific mechanisms and pathways that mitochondria regulate in NMRs, nor about how these roles vary between tissues with divergent metabolic demands in hypoxia. Hang’s theses uncovered mechanisms via which mitochondria regulate oxidative phosphorylation (OXPHOS), reactive oxygen species (ROS), and calcium, and the impact of these mechanisms on hypoxia/ischemia tolerance in NMR interscapular brown adipose tissue (iBAT), brain, and skeletal muscle. Specifically: 1) In hypoxia, iBAT mitochondria significantly suppress respiration (by 45-70%) and rate of calcium uptake. These functional changes were accompanied by rapid reductions in the expression of OXPHOS and UCP1 proteins, which was likely mediated by mitochondrial membrane remodeling, including the activation of mitochondrial fission and inhibition of apoptosis. 2) NMR brain mitochondria have a very high capacity to buffer calcium. Elevated mitochondrial calcium suppresses the oxygen consumption rate without compromising membrane integrity in NMRs but not in mice. The mechanism underlying this enhanced capacity likely involves the occurrence of larger and more interconnected mitochondrial networks in NMR brain. As a result, NMR brain is better able to regulate redox state, minimize excitotoxity (i.e., glutamate, calcium), and retain OXPHOS function under in vitro ischemia than mouse brain. 3) Skeletal muscle mitochondria exhibit a mild decrease in OXPHOS function but reduce mitochondrial superoxide (O2·−) emission in acute and chronic hypoxia, which may support continuous exercise in intermittent hypoxic burrow systems in nature. Overall, these results suggested that NMR mitochondria play key roles in maintaining essential functions (e.g., brain function, physical activity), and also suppressing non-essential functions (e.g., thermogenesis) in a tissue-specific fashion to minimize the oxygen consumption and hypoxia-induced cell damage.
Most adult mammals are highly sensitive to reduced oxygen availability; however, some species have evolved to live in hypoxic environments. Naked mole-rats (NMRs, Heterocephalus glaber) are among the most hypoxia-tolerant mammals and rapidly reduce whole animal oxygen consumption during hypoxia. Mitochondria are cellular oxygen sensors, major consumers of oxygen, and regulators of numerous cellular signalling pathways, and thus play key roles in cellular responses to hypoxia. However, little is known about the specific mechanisms and pathways that mitochondria regulate in NMRs, nor about how these roles vary between tissues with divergent metabolic demands in hypoxia. Hang’s theses uncovered mechanisms via which mitochondria regulate oxidative phosphorylation (OXPHOS), reactive oxygen species (ROS), and calcium, and the impact of these mechanisms on hypoxia/ischemia tolerance in NMR interscapular brown adipose tissue (iBAT), brain, and skeletal muscle. Specifically: 1) In hypoxia, iBAT mitochondria significantly suppress respiration (by 45-70%) and rate of calcium uptake. These functional changes were accompanied by rapid reductions in the expression of OXPHOS and UCP1 proteins, which was likely mediated by mitochondrial membrane remodeling, including the activation of mitochondrial fission and inhibition of apoptosis. 2) NMR brain mitochondria have a very high capacity to buffer calcium. Elevated mitochondrial calcium suppresses the oxygen consumption rate without compromising membrane integrity in NMRs but not in mice. The mechanism underlying this enhanced capacity likely involves the occurrence of larger and more interconnected mitochondrial networks in NMR brain. As a result, NMR brain is better able to regulate redox state, minimize excitotoxity (i.e., glutamate, calcium), and retain OXPHOS function under in vitro ischemia than mouse brain. 3) Skeletal muscle mitochondria exhibit a mild decrease in OXPHOS function but reduce mitochondrial superoxide (O2·−) emission in acute and chronic hypoxia, which may support continuous exercise in intermittent hypoxic burrow systems in nature. Overall, these results suggested that NMR mitochondria play key roles in maintaining essential functions (e.g., brain function, physical activity), and also suppressing non-essential functions (e.g., thermogenesis) in a tissue-specific fashion to minimize the oxygen consumption and hypoxia-induced cell damage.