Mitochondria Homeostasis and Oxidant/Antioxidant Balance in Skeletal Muscle—Do Myokines Play a Role?

Abstract

Mitochondria are the cellular powerhouses that generate adenosine triphosphate (ATP) to substantiate various biochemical activities. Instead of being a static intracellular structure, they are dynamic organelles that perform constant structural and functional remodeling in response to different metabolic stresses. In situations that require a high ATP supply, new mitochondria are assembled (mitochondrial biogenesis) or formed by fusing the existing mitochondria (mitochondrial fusion) to maximize the oxidative capacity. On the other hand, nutrient overload may produce detrimental metabolites such as reactive oxidative species (ROS) that wreck the organelle, leading to the split of damaged mitochondria (mitofission) for clearance (mitophagy). These vital processes are tightly regulated by a sophisticated quality control system involving energy sensing, intracellular membrane interaction, autophagy, and proteasomal degradation to optimize the number of healthy mitochondria. The effective mitochondrial surveillance is particularly important to skeletal muscle fitness because of its large tissue mass as well as its high metabolic activities for supporting the intensive myofiber contractility. Indeed, the failure of the mitochondrial quality control system in skeletal muscle is associated with diseases such as insulin resistance, aging, and muscle wasting. While the mitochondrial dynamics in cells are believed to be intrinsically controlled by the energy content and nutrient availability, other upstream regulators such as hormonal signals from distal organs or factors generated by the muscle itself may also play a critical role. It is now clear that skeletal muscle actively participates in systemic energy homeostasis via producing hundreds of myokines. Acting either as autocrine/paracrine or circulating hormones to crosstalk with other organs, these secretory myokines regulate a large number of physiological activities including insulin sensitivity, fuel utilization, cell differentiation, and appetite behavior. In this article, we will review the mechanism of myokines in mitochondrial quality control and ROS balance, and discuss their translational potential.

Biological Aspects of Selected Myokines in Skeletal Muscle: Focus on Aging

“…Reducing the insulin/IGF1 receptor pathway, well known to promote longevity, also improves sarcopenia [22]. In animal models, mitochondrial dysfunction (fragmentation and/or decreased number) may also contribute to the onset of sarcopenia: in rodents, there is an age-dependent reduction in mitochondrial mass associated with a change in morphology; in nematodes, there is an agedependent fragmentation of mitochondria that precedes sarcomeric disorganization [23]. The lack of stem cells in worms and flies provides the opportunity to study processes that promote muscle maintenance without the confounding influence of muscle regeneration related to stem cell activity [20].…”

High-Fat Diet-Induced Mitochondrial Dysfunction Promotes Genioglossus Injury – A Potential Mechanism for Obstructive Sleep Apnea with Obesity

“…Mitochondrial dysfunction can lead to ROS overproduction, causing damage to cells and tissues. 26 To evaluate the effects of PA on mitochondrial ROS levels, MitoSOX Red (a mitochondrial superoxide indicator) was used for immunofluorescence staining. PA at 300 μ M significantly increased mitochondrial ROS accumulation in C2C12 myotubes ( p < 0.001) ( Figure 8A and B ).…”

“…Mitochondrial dysfunction contributes to the excessive accumulation of reactive oxygen species (ROS) and oxidative stress, which causes oxidative damage to major cellular structures (in particular, the plasma membrane, proteins and DNA) and leads to apoptosis. 26 In HFD-induced obesity, oxidative damage accompanied by mitochondrial impairment has been found, which is a critical factor for skeletal muscle dysfunction. 27 , 28 Our previous work that focused on OSA demonstrated that ROS overproduction caused by hypoxia contributed to pyroptosis in myoblasts and might be a critical pathogenesis of OSA.…”

The Nucleus/Mitochondria-Shuttling LncRNAs Function as New Epigenetic Regulators of Mitophagy in Cancer

“…In addition, mitophagy regulates the elimination of sperm mitochondria, thereby avoiding the inheritance of paternal mitochondrial DNA (mtDNA; Rojansky et al, 2016 ; Song et al, 2016 ). Since mitophagy plays a crucial role in maintaining mitochondrial homeostasis ( Bin-Umer et al, 2014 ), it is not surprising that defective, inadequate, or excessive mitophagy can result in pathological conditions ( Palikaras et al, 2017 ), such as neurodegenerative disease ( Um and Yun, 2017 ; Tran and Reddy, 2020 ; Wang et al, 2021 ), cardiovascular disease ( Billia et al, 2011 ; Zhang W. et al, 2016 ; Zhang et al, 2017 ; Chang et al, 2020 ), metabolic disorders ( He et al, 2021 ; Pang et al, 2021 ; Zia et al, 2021 ), inflammation ( Sliter et al, 2018 ; Lee et al, 2020 ), liver disease ( Ke, 2020 ; Kouroumalis et al, 2021 ), aging ( Richard et al, 2013 ; Cornelissen et al, 2018 ), and cancer.…”