Work those mitochondria, the powerhouse of muscle cells

David HoodDavid Hood (left), Professor in the School of Kinesiology & Health Science, Director of York’s Muscle Health Research Centre and Canada Research Chair in Cell Physiology has had a stellar year with his research focus on how proteins affect mitochondria in muscle cells and in metabolism.

The paper, “Sirtuin 1-Mediated Effects of Exercise and Resveratrol on Mitochondrial Biogenesis”, was chosen as one of the best research papers published in 2013 in The Journal of Biological Chemistry. It was authored by Hood’s graduate student Keir J. Menzies of the Department of Biology and a recipient of a doctoral award from the Canadian Institutes of Health Research, and grad students Kaustabh Singh and Ayesha Saleem of the School of Kinesiology and Health Science.  All of the authors conduct research in York’s Muscle Health Research Centre.

“It is an honour to have our manuscript chosen as one of the best papers of the year in this prestigious journal, particularly within “Metabolism”, where there is a very high intensity of research being undertaken worldwide.  This accomplishment is a real credit to the talents of Keir Menzies and his excellent work ethic,” says Hood.

The core of Dr. Hood’s research is mitochondria, tiny organelles that are responsible for energy production in all cells, often referred to as the “powerhouse of the cell”. Aging and disease causes mitochondria within cells to shrink and fragment, and leads to cell damage and the degeneration of muscle cells. However, Hood and his students have found that exercise promotes the mitochondria in the cells to expand and thus have a better distribution within the muscle. The more you exercise, the better you can distribute energy throughout your muscles.

In order for mitochondria to undergo mitochondrial biogenesis (MB), the process that strengthens the network, proteins are necessary. To study what starts the process of strengthening, Hood and his students took a step back in the chain of events.

Mitochondrion

Courtesy of Journal of International Innovation

The naturally-occurring protein Sirtuin 1, when combined with exercise and activated by Resveratrol (found in the skins of red grapes, and shown to improve the longevity of mice), creates a synergy that improves the MB process exponentially and helps extend the mitochondrial network. When the protein Sirt-1 is deficient, less exponential mitochondrial growth has been shown, explaining why it might take some people longer to get used to working out and seeing the results of their efforts. Both Sirt-1 and Resveratrol have to be present for a synergist increase in mitochondria to occur within muscle, creating a more dramatic result.

More recent findings from Hood’s lab, led by Ayesha Saleem, have been groundbreaking in the protein world. The p53 protein was previously never connected with metabolism-related diseases because it was known as a cancer suppressor. However, p53 also controls mitochondria. If a person has no p53, they have less active mitochondria, which means less energy and less adaptation to exercise. This can contribute to excessive fatigue experienced by some cancer patients – for whom exercise will not improve energy levels. Keeping these findings in mind when designing exercise programs may assist people with less active mitochondria to derive more benefits from exercise.

Heather Carter (left), David Hood, Sobia Iqbal and Anna Vainshtein (right)Heather Carter (left), David Hood, Sobia Iqbal and Anna Vainshtein (right) currently study the synthesis and breakdown of mitochondria in muscle as it adapts to exercise.

“Ayesha Saleem did a wonderful job defining a surprising new and unique role for p53 in the adaptation of muscle to exercise,” says Hood.

These findings appear in a newly published article, “p53 is Necessary for the Adaptive Changes in Cellular Milieu Subsequent to an Acute Bout of Endurance Exercise”, in the American Journal of Physiology, Cell Physiology (February 2014).

Hood will continue to oversee a busy lab as he recently received $589,685 over five years from CIHR to examine how exercise can improve musculoskeletal health during the aging process. His research will examine the reasons for the reduced mitochondrial content and function in aging muscle. While mitochondria are known as the energy centres of the cell, they can also be responsible for the synthesis of harmful reactive oxygen species, free radical molecules which cause muscle cell death, when produced in excessive amounts. Such is the case in aging muscle. Hood’s research will also examine how exercise can attenuate this mitochondrial dysfunction and improve muscle health as people age.

Hood’s final words? “Good muscle health is vital to staying healthy and enjoying a better quality of life in our later years, so let’s stay active!”