Mitochondrial Bioenergetics and Turnover during Chronic Muscle Disuse

Abstract

Periods of muscle disuse promote marked mitochondrial alterations that contribute to the impaired metabolic health and degree of atrophy in the muscle. Thus, understanding the molecular underpinnings of muscle mitochondrial decline with prolonged inactivity is of considerable interest. There are translational applications to patients subjected to limb immobilization following injury, illness-induced bed rest, neuropathies, and even microgravity. Studies in these patients, as well as on various pre-clinical rodent models have elucidated the pathways involved in mitochondrial quality control, such as mitochondrial biogenesis, mitophagy, fission and fusion, and the corresponding mitochondrial derangements that underlie the muscle atrophy that ensues from inactivity. Defective organelles display altered respiratory function concurrent with increased accumulation of reactive oxygen species, which exacerbate myofiber atrophy via degradative pathways. The preservation of muscle quality and function is critical for maintaining mobility throughout the lifespan, and for the prevention of inactivity-related diseases. Exercise training is effective in preserving muscle mass by promoting favourable mitochondrial adaptations that offset the mitochondrial dysfunction, which contributes to the declines in muscle and whole-body metabolic health. This highlights the need for further investigation of the mechanisms in which mitochondria contribute to disuse-induced atrophy, as well as the specific molecular targets that can be exploited therapeutically.

Protective Effects of the Chalcone-Based Derivative AN07 on Inflammation-Associated Myotube Atrophy Induced by Lipopolysaccharide

“…Mitochondrial respiration is the most important contributor of cellular energy. The dysfunction of mitochondria results in energy stress and is highly correlated with impairment of skeletal muscle mass and function [ 44 ]. Previous studies have demonstrated that oxidative stress induces mitochondrial dysfunction via the depolarization of inner mitochondrial membrane potential and subsequent impairment of oxidative phosphorylation [ 45 ].…”

Mori Ramulus Suppresses Hydrogen Peroxide-Induced Oxidative Damage in Murine Myoblast C2C12 Cells through Activation of AMPK

“…Oxidative stress can cause damage to various intracellular organelles and macromolecules, failure to restore sustained oxidative stress eventually induces apoptosis, resulting in tissue and organ injury [10,30]. In particular, in skeletal muscle susceptible to oxidative stress, mitochondrial impairment serves as an initiation signal for activation of the endogenous apoptosis pathway [3,5,31,32]. In addition, oxidatively damaged DNA induces genetic mutations, and disrupts the homeostasis of muscle function, which not only causes muscle damage, but also causes the failure of inducing differentiation of myoblasts into muscle cells [8,33].…”

Prevention of muscle atrophy in ICU patients without nerve injury by neuromuscular electrical stimulation: a randomized controlled study

“…Patients admitted to the emergency ICU of our hospital from December 2020 to June 2021 were included in the study. Inclusion criteria were: (1) patients who were conscious; (2) with no central and peripheral nervous system injury; (3) no acute exacerbation; (4) expected to be treated in ICU for more than 1 week, and training could be completed on at least one side of the lower limbs. Exclusion criteria were the following: patients in a coma, inability to cooperate with treatment, original limb function defect or neuromuscular disease, other defects, wound or external fixation of the treatment area, patients with sarcopenia (calf circumference < 34 cm for men and < 33 cm for women, and grip strength < 28 kg for men and < 18 kg for women) [20], and other contraindications of NMES, such as high fever, cardiac pacemaker implantation, severe arrhythmia, etc.…”

“…Extensive muscle atrophy is a common occurrence in patients who are bedridden or immobilized [ 1 , 2 ], while the degree of muscle atrophy is positively correlated with the time spent in bed [ 1 ]. Also, the incidence is higher in intensive care unit (ICU) inpatients.…”