New Insights into Molecular Mechanisms Mediating Adaptation to Exercise; A Review Focusing on Mitochondrial Biogenesis, Mitochondrial Function, Mitophagy and Autophagy

Abstract

Exercise itself is fundamental for good health, and when practiced regularly confers a myriad of metabolic benefits in a range of tissues. These benefits are mediated by a range of adaptive responses in a coordinated, multi-organ manner. The continued understanding of the molecular mechanisms of action which confer beneficial effects of exercise on the body will identify more specific pathways which can be manipulated by therapeutic intervention in order to prevent or treat various metabolism-associated diseases. This is particularly important as exercise is not an available option to all and so novel methods must be identified to confer the beneficial effects of exercise in a therapeutic manner. This review will focus on key emerging molecular mechanisms of mitochondrial biogenesis, autophagy and mitophagy in selected, highly metabolic tissues, describing their regulation and contribution to beneficial adaptations to exercise.

Insight Into the Metabolic Adaptations of Electrically Pulse-Stimulated Human Myotubes Using Global Analysis of the Transcriptome and Proteome

“…Thus, the available evidence suggests that ROS production as a result of exercise-mediated oxidative stress could be a requirement for skeletal muscle metabolic adaptations, and that compensatory mechanisms are induced to maintain the redox balance, protecting the cell against deleterious effects of contraction-mediated oxidative stress. Moreover, autophagy, which is a self-degradative process essential for providing new source of energy and disposal of misfolded proteins and damaged organelles including mitochondria (mitophagy) ( Glick et al, 2010 ; Roberts and Markby, 2021 ), has been suggested to be initiated by ROS and AMPK in exercising muscle ( Glick et al, 2010 ; Hardie, 2011 ; Ferraro et al, 2014 ; Vainshtein and Hood, 2015 ). It is known that the raise in AMP:ATP-ratio during in vivo exercise and ex vivo skeletal muscle contraction activates AMPK ( Hardie and SakamotoAMPK, 2006 ; Kjøbsted et al, 2018 ).…”

“…This stimulation of skeletal muscle by exercise bouts is integrated by a multitude of complex signaling networks, where the physiological response varies by the frequency, intensity, and duration of the exercise ( Hoppeler et al, 2011 ) as well as intrinsic factors such as age and body composition ( Egan and Zierath, 2013 ). From a metabolic point of view, exercise-mediated adaptations in skeletal muscle are reflected by an increase in mitochondrial biogenesis ( Holloszy and Coyle, 1984 ; Roberts and Markby, 2021 ), improved oxidative capacity of glucose and fatty acids as well as enhanced insulin-stimulated glucose uptake ( Turcotte and Fisher, 2008 ). Moreover, it is increasingly evident that skeletal muscle can produce and secret cytokines and other peptides (referred to as myokines) in response to physical exercise and muscle contraction ( Norheim et al, 2011 ; Pedersen and Febbraio, 2012 ).…”

Exercise Improves Redox Homeostasis and Mitochondrial Function in White Adipose Tissue

“…It was demonstrated that strength training increased browning process-related genes in the subcutaneous adipose tissue, independently of changes in body weight [ 59 ]. Exercise induces metabolic improvements by the enhancement of mitochondrial respiration and ATP production in several tissues, including WAT [ 60 ]. However, no evidence was found demonstrating the role of exercise in the relationship between mitochondrial function and redox homeostasis in WAT.…”

Could Repeated Cardio-Renal Injury Trigger Late Cardiovascular Sequelae in Extreme Endurance Athletes?

“…Importantly, not only skeletal muscle mitochondria but also mitochondria in other organs including the heart and kidney are affected by endurance exercise, for example by preventing the decrease in mitochondrial NADH-cytochrome-C reductase and cytochrome oxidase activities in those organs [111]. Although the mechanisms for the transfer of the mitochondrial effects to tissues distant from skeletal muscles are not fully understood yet, the pronounced impact of exercise on mitochondria in many tissues becomes increasingly established and may explain many of the health effects of exercise [112].…”

“…There is growing evidence supporting an important role of exercise-induced protective effects (e.g., in the prevention of metabolic, cardiovascular, and neurodegenerative diseases), at least partly mediated by autophagy, mitophagy, and mitochondrial biogenesis [112]. Evidence is also accumulating that chronic moderate endurance exercise can be protective for AKI [113].…”