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

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 179
Author(s):  
Brian Pak Shing Pang ◽  
Wing Suen Chan ◽  
Chi Bun Chan
Keyword(s):  
Skeletal Muscle ◽  
Quality Control ◽  
Control System ◽  
Energy Content ◽  
Mitochondrial Dynamics ◽  
Critical Role ◽  
Oxidative Capacity ◽  
Quality Control System ◽  
Mitochondrial Quality Control ◽  
Tissue Mass

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.

Short term intensified training temporarily impairs mitochondrial respiratory capacity in elite endurance athletes

2021 ◽  
Author(s):  
Daniele A. Cardinale ◽  
Kasper D. Gejl ◽  
Kristine Grøsfjeld Petersen ◽  
Joachim Nielsen ◽  
Niels Ørtenblad ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Quality Control ◽  
Oxidative Capacity ◽  
Endurance Athletes ◽  
Training Period ◽  
Moderate Intensity ◽  
Mitochondrial Quality Control ◽  
Quality Control Program ◽  
Mitochondrial Oxidative Capacity ◽  
Mitochondrial Respiratory

Aim: The maintenance of healthy and functional mitochondria is the result of a complex mitochondrial turnover and herein quality-control program which includes both mitochondrial biogenesis and autophagy of mitochondria. The aim of this study was to examine the effect of an intensified training load on skeletal muscle mitochondrial quality control in relation to changes in mitochondrial oxidative capacity, maximal oxygen consumption and performance in highly trained endurance athletes. Methods: 27 elite endurance athletes performed high intensity interval exercise followed by moderate intensity continuous exercise 3 days per week for 4 weeks in addition to their usual volume of training. Mitochondrial oxidative capacity, abundance of mitochondrial proteins, markers of autophagy and antioxidant capacity of skeletal muscle were assessed in skeletal muscle biopsies before and after the intensified training period. Results: The intensified training period increased several autophagy markers suggesting an increased turnover of mitochondrial and cytosolic proteins. In permeabilized muscle fibers, mitochondrial respiration was ~20 % lower after training although some markers of mitochondrial density increased by 5-50%, indicative of a reduced mitochondrial quality by the intensified training intervention. The antioxidative proteins UCP3, ANT1, and SOD2 were increased after training, whereas we found an inactivation of aconitase. In agreement with the lower aconitase activity, the amount of mitochondrial LON protease that selectively degrades oxidized aconitase, was doubled. Conclusion: Together, this suggests that mitochondrial respiratory function is impaired during the initial recovery from a period of intensified endurance training while mitochondrial quality control is slightly activated in highly trained skeletal muscle.

scholarly journals Insertion Defects of Mitochondrially Encoded Proteins Burden the Mitochondrial Quality Control System

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 172 ◽  
Author(s):  
Braulio Vargas Möller-Hergt ◽  
Andreas Carlström ◽  
Tamara Suhm ◽  
Martin Ott
Keyword(s):  
Quality Control ◽  
Control System ◽  
Mitochondrial Protein ◽  
Quality Control System ◽  
Yeast Cells ◽  
Mitochondrial Quality Control ◽  
Protein Insertion ◽  
Mitochondrial Proteome ◽  
Proteotoxic Stress ◽  
Membrane Protein Insertion

The mitochondrial proteome contains proteins from two different genetic systems. Proteins are either synthesized in the cytosol and imported into the different compartments of the organelle or directly produced in the mitochondrial matrix. To ensure proteostasis, proteins are monitored by the mitochondrial quality control system, which will degrade non-native polypeptides. Defective mitochondrial membrane proteins are degraded by membrane-bound AAA-proteases. These proteases are regulated by factors promoting protein turnover or preventing their degradation. Here we determined genetic interactions between the mitoribosome receptors Mrx15 and Mba1 with the quality control system. We show that simultaneous absence of Mrx15 and the regulators of the i-AAA protease Mgr1 and Mgr3 provokes respiratory deficiency. Surprisingly, mutants lacking Mrx15 were more tolerant against proteotoxic stress. Furthermore, yeast cells became hypersensitive against proteotoxic stress upon deletion of MBA1. Contrary to Mrx15, Mba1 cooperates with the regulators of the m-AAA and i-AAA proteases. Taken together, these results suggest that membrane protein insertion and mitochondrial AAA-proteases are functionally coupled, possibly reflecting an early quality control step during mitochondrial protein synthesis.

scholarly journals Human skeletal muscle mitochondrial dynamics in relation to oxidative capacity and insulin sensitivity

Diabetologia ◽  
2020 ◽  
Author(s):  
Alexandre Houzelle ◽  
Johanna A. Jörgensen ◽  
Gert Schaart ◽  
Sabine Daemen ◽  
Nynke van Polanen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Quality Control ◽  
Insulin Sensitivity ◽  
Aerobic Capacity ◽  
Mitochondrial Dynamics ◽  
Oxidative Capacity ◽  
Protein Balance ◽  
Diabetes Patients

Abstract Aims/hypothesis Mitochondria operate in networks, adapting to external stresses and changes in cellular metabolic demand and are subject to various quality control mechanisms. On the basis of these traits, we here hypothesise that the regulation of mitochondrial networks in skeletal muscle is hampered in humans with compromised oxidative capacity and insulin sensitivity. Methods In a cross-sectional design, we compared four groups of participants (selected from previous studies) ranging in aerobic capacity and insulin sensitivity, i.e. participants with type 2 diabetes (n = 11), obese participants without diabetes (n = 12), lean individuals (n = 10) and endurance-trained athletes (n = 12); basal, overnight fasted muscle biopsies were newly analysed for the current study and we compared the levels of essential mitochondrial dynamics and quality control regulatory proteins in skeletal muscle tissue. Results Type 2 diabetes patients and obese participants were older than lean participants and athletes (58.6 ± 4.0 and 56.7 ± 7.2 vs 21.8 ± 2.5 and 25.1 ± 4.3 years, p < 0.001, respectively) and displayed a higher BMI (32.4 ± 3.7 and 31.0 ± 3.7 vs 22.1 ± 1.8 and 21.0 ± 1.5 kg/m2, p < 0.001, respectively) than lean individuals and endurance-trained athletes. Fission protein 1 (FIS1) and optic atrophy protein 1 (OPA1) protein content was highest in muscle from athletes and lowest in participants with type 2 diabetes and obesity, respectively (FIS1: 1.86 ± 0.79 vs 0.79 ± 0.51 AU, p = 0.002; and OPA1: 1.55 ± 0.64 vs 0.76 ± 0.52 AU, p = 0.014), which coincided with mitochondrial network fragmentation in individuals with type 2 diabetes, as assessed by confocal microscopy in a subset of type 2 diabetes patients vs endurance-trained athletes (n = 6). Furthermore, lean individuals and athletes displayed a mitonuclear protein balance that was different from obese participants and those with type 2 diabetes. Mitonuclear protein balance also associated with heat shock protein 60 (HSP60) protein levels, which were higher in athletes when compared with participants with obesity (p = 0.048) and type 2 diabetes (p = 0.002), indicative for activation of the mitochondrial unfolded protein response. Finally, OPA1, FIS1 and HSP60 correlated positively with aerobic capacity (r = 0.48, p = 0.0001; r = 0.55, p < 0.001 and r = 0.61, p < 0.0001, respectively) and insulin sensitivity (r = 0.40, p = 0.008; r = 0.44, p = 0.003 and r = 0.48, p = 0.001, respectively). Conclusions/interpretation Collectively, our data suggest that mitochondrial dynamics and quality control in skeletal muscle are linked to oxidative capacity in humans, which may play a role in the maintenance of muscle insulin sensitivity. Clinical Trial registry numbers NCT00943059, NCT01298375 and NL1888

scholarly journals Azidothymidine-triphosphate impairs mitochondrial dynamics by disrupting the quality control system

Redox Biology ◽  
2017 ◽  
Vol 13 ◽  
pp. 407-417 ◽  
Author(s):  
Ryosuke Nomura ◽  
Takeya Sato ◽  
Yuka Sato ◽  
Jeffrey A. Medin ◽  
Shigeki Kushimoto ◽  
...  
Keyword(s):  
Quality Control ◽  
Control System ◽  
Mitochondrial Dynamics ◽  
Quality Control System

scholarly journals Role of gp130 in basal and exercise-trained skeletal muscle mitochondrial quality control

2018 ◽  
Vol 124 (6) ◽  
pp. 1456-1470 ◽  
Author(s):  
Dennis K. Fix ◽  
Justin P. Hardee ◽  
Song Gao ◽  
Brandon N. VanderVeen ◽  
Kandy T. Velázquez ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Quality Control ◽  
Exercise Training ◽  
Intracellular Signaling ◽  
Metabolic Response ◽  
Muscle Protein ◽  
Mitochondrial Dynamics ◽  
Peroxisome Proliferator ◽  
Skeletal Muscle Protein ◽  
Mitochondrial Quality Control

The IL-6 cytokine family activates intracellular signaling pathways through glycoprotein-130 (gp130), and this signaling has established regulatory roles in muscle glucose metabolism and proteostasis. Although the IL-6 family has been implicated as myokines regulating the muscles’ metabolic response to exercise, gp130’s role in mitochondrial quality control involving fission, fusion, mitophagy, and biogenesis is not well understood. Therefore, we examined gp130’s role in basal and exercise-trained muscle mitochondrial quality control. Muscles from C57BL/6, skeletal muscle-specific gp130 knockout (KO) mice, and C2C12 myotubes, were examined. KO did not alter treadmill run-to-fatigue or indices of mitochondrial content [cytochrome- c oxidase (COX) activity] or biogenesis (AMPK, peroxisome proliferator-activated receptor-γ coactivator-1α, mitochondrial transcription factor A, and COX IV). KO increased mitochondrial fission 1 protein (FIS-1) while suppressing mitofusin-1 (MFN-1), which was recapitulated in myotubes after gp130 knockdown. KO induced ubiquitin-binding protein p62, Parkin, and ubiquitin in isolated mitochondria from gastrocnemius muscles. Knockdown of gp130 in myotubes suppressed STAT3 and induced accumulation of microtubule-associated protein-1 light chain 3B (LC3)-II relative to LC3-I. Suppression of myotube STAT3 did not alter FIS-1 or MFN-1. Exercise training increased muscle gp130 and suppressed STAT3. KO did not alter the exercise-training induction of COX activity, biogenesis, FIS-1, or Beclin-1. KO increased MFN-1 and suppressed 4-hydroxynonenal after exercise training. These findings suggest a role for gp130 in the modulation of mitochondrial dynamics and autophagic processes. NEW & NOTEWORTHY Although the IL-6 family of cytokines has been implicated in the regulation of skeletal muscle protein turnover and metabolism, less is understood about its role in mitochondrial quality control. We examined the glycoprotein-130 receptor in the regulation of skeletal muscle mitochondria quality control in the basal and exercise-trained states. We report that the muscle glycoprotein-130 receptor modulates basal mitochondrial dynamics and autophagic processes and is not necessary for exercise-training mitochondrial adaptations to quality control.

scholarly journals Different dynamic movements of wild-type and pathogenic VCPs and their cofactors to damaged mitochondria in a Parkin-mediated mitochondrial quality control system

2013 ◽  
Vol 18 (12) ◽  
pp. 1131-1143 ◽  
Author(s):  
Yoko Kimura ◽  
Junpei Fukushi ◽  
Seiji Hori ◽  
Noriyuki Matsuda ◽  
Kei Okatsu ◽  
...  
Keyword(s):  
Quality Control ◽  
Control System ◽  
Quality Control System ◽  
Wild Type ◽  
Mitochondrial Quality Control
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