Seminar: Variable OXPHOS efficiency in skeletal muscle: Proton leaks, ROS and glutathione redox
Variable OXPHOS efficiency in skeletal muscle: Proton leaks, ROS and glutathione redox
v/ Professor Mary-Ellen Harper, Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa
7 December 2018
14:00-15:00: Seminar and discussion
15:00-16:00: Post seminar servings and socializing
Oxidative phosphorylation (OXPHOS) is estimated to account for roughly 90% of cellular ATP production, though this can vary between cell types, metabolic conditions, and disease states. The efficiency of ATP production by OXPHOS is highly variable, and efficiency can be expressed as units ATP produced per unit of substrate oxidized, or as units ATP produced per unit of oxygen consumed.
Efficiency of OXPHOS is affected by site of electron entry into the electron transport system. It also is greatly affected by proton leak uncoupling, and other routes of proton return to the mitochondrial matrix. Proton leak has poorly understood mechanisms, but includes the uncoupling proteins and the adenine nucleotide translocator (ANT). Beyond decreasing the efficiency of OXPHOS, proton leak can decrease the emission of reactive oxygen species (ROS) from the electron transport system by lowering protonmotive force. High levels of ROS can cause damage to cellular lipids, proteins, DNA and RNA. However low levels of ROS are important in cell signaling processes.
Glutathione is the major non-protein antioxidant in cells and in mitochondria. It also plays important roles in the post-translational modification of protein thiols, and this can protect the proteins from further damage, and can modify the function of the proteins. The latter concepts will be covered in this seminar, and experimental findings from studies of mouse and human skeletal muscles will be presented.
Also presented will be findings from our clinical translational studies which demonstrate the importance of skeletal muscle OXPHOS in diet-sensitive versus diet-resistant obesity.
Ghadi Antoun, Fiona McMurray, A. Brianne Thrush, David A. Patten, Alyssa C. Peixoto, Ruth S. Slack, Ruth McPherson, Robert Dent, Mary-Ellen Harper. Impaired mitochondrial oxidative phosphorylation and supercomplex assembly in rectus abdominis muscle of diabetic obese individuals. Diabetologia (2015) 58:2861–2866.
AB Thrush, G Antoun, M Nikpay, DA Patten, C DeVlugt, J-F Mauger, BL Beauchamp, P Lau, R Reshke, É Doucet, P Imbeault, R Boushel, D Gibbings, J Hager, A Valsesia, RS Slack, OY Al-Dirbashi, R Dent, R McPherson, and M-E Harper. Diet-resistant obesity is characterized by a distinct plasma proteomic signature and impaired muscle fiber metabolism. International Journal of Obesity (2018) 42, 353–362.
Georges N. Kanaan, Bianca Ichim, Lara Gharibeh, Wael Maharsy, David A. Patten, Jian Ying Xuan, Arkadiy Reunov, Philip Marshall, John Veinot, Keir Menzies, Mona Nemer, Mary-Ellen Harper. Glutaredoxin-2 controls cardiac mitochondrial dynamics and energetics in mice, and protects against human cardiac pathologies. Redox Biology 14 (2018) 509–521.
Professor Mary-Ellen Harper received an undergraduate degree in Nutrition from the University of Guelph prior to completing her PhD in Biochemistry, supervised by Dr. John Patrick and Dr. Jean Himms-Hagen, at the University of Ottawa. Dr. Harper then trained as a Postdoctoral Fellow in Dr. Martin Brand’s laboratory in the Department of Biochemistry at the University of Cambridge (UK). In 1995 Dr. Harper established her Mitochondrial Bioenergetics research laboratory at the University of Ottawa Faculty of Medicine.
Dr. Harper’s research focuses on mechanisms that impact the efficiency of energy conversion pathways in mitochondria. Changes in the efficiency of energy conversion can affect the development of diseases and metabolic dysfunction, and her research probes mechanisms in the context of obesity, diabetes, heart failure and cancer. Experimental approaches span from molecular in vitro studies, to mouse models, and to integrative studies in patient populations. Her current laboratory team includes three postdoctoral fellows, three PhD students, four undergraduate research students, and a technician.
Research has been funded by Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council (NSERC), Heart and Stroke Foundation, National Institutes of Health (NIH), Canadian Cancer Society Research Institute, and the Canadian Foundation for Innovation (CFI). In 2015, she was the recipient of a CIHR Foundations Award to support research on ‘Mitochondrial Bioenergetics and Redox Biology in Obesity and Related Disease’. In 2018 she received the Departmental Researcher of the Year award. She currently holds a University Research Chair in Mitochondrial Bioenergetics. Dr. Harper is the Principal Investigator, and Director of the NSERC-funded Metabolomics Advanced Training and International Exchange (MATRIX) training program, based at Universities of Ottawa, McGill and Montréal.
Dr. Harper teaches at the undergraduate and graduate levels and serves on many scientific mentorship and other committees at the University of Ottawa. She has published over 160 peer-reviewed papers.
Auditorium 1, August Krogh Building, Universitetsparken 13, DK-2100 Copenhagen
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Jonas Møller Kristensen, firstname.lastname@example.org, phone +45 3533 4776
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