scholarly journals p53 regulates skeletal muscle mitophagy and mitochondrial quality control following denervation-induced muscle disuse

2021 ◽  
pp. 101540
Author(s):  
Jonathan M. Memme ◽  
Ashley N. Oliveira ◽  
David A. Hood
Keyword(s):  
Skeletal Muscle ◽  
Quality Control ◽  
Mitochondrial Quality Control ◽  
Muscle Disuse

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 OR-043 UPRmt and mitophagy are selectively activated depending on muscle fiber types in insulin resistant rats

2018 ◽  
Vol 1 (2) ◽  
Author(s):  
Can Li ◽  
Nan Li ◽  
Yong Zhang
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Quality Control ◽  
Muscle Fiber ◽  
Slow Muscle ◽  
Muscle Fiber Types ◽  
Fiber Types ◽  
Mitochondrial Quality Control ◽  
Insulin Resistant ◽  
Related Proteins

Objective To investigate how different skeletal muscle fiber types affect development of insulin resistance, and to explore the role of mitochondrial quality control system, especially mitochondrial unfolded protein response (UPRmt) and mitophagy, in response to metabolic stresses. Methods Male Wistar rats were randomly divided into 2 groups: fed with the normal diet for 8 weeks (Con), and fed with 45% high-fat diet for 8 weeks (IR). Fasting blood glucose (FBG), fasting insulin (FIN) and oral glucose tolerance test (OGTT) were used to identify insulin resistance model. Gastrocnemius (GC), soleus (SOL) and tibialis anterior (TA) muscle were isolated, and RT-qPCR was used to determine the expression of Myhc7, Myhc4. Oxygraph-2k was used to determine the mitochondrial State 3 (ST3), State 4(ST4) respiration and respiration control rate (RCR). JC-1 probe was used to measure mitochondrial membrane potential. Western Blot was used to determine the expressions of marker proteins of muscle fiber types (Myhc4, Myhc7), UPRmt related proteins (Hsp60, Hsp70) and mitophagy related proteins (Pink1, LC3). Results Compared with Con group, in IR group, FBG (7.1±1.27 vs. 5.4±0.43，p＜0.05), FIN (19.4±5.2 vs. 31.6±6.7，p＜0.05 ) and OGTT (area under the curve, about 31.7% increases, p＜0.05) were significantly higher. Myhc4 mRNA (relative fold about 55.6% increases) and protein expression (about 33.9% increases, p＜0.05) were significantly higher in GC. Myhc4 protein expression was significantly higher in GC (about 60.5% increases, p＜0.05). While Myhc7 mRNA expression (about 51.1% decreases, p＜0.05) was significantly lower in SOL. Compared with Con group, in IR group, mitochondrial RCR in SOL muscle was significantly lower (about 22.5% decreases, p＜0.05). Furthermore, the expression of HSP60 (about 36.7% increases，p＜0.05) and HSP70 (about 44.3% increases，p＜0.05) was significantly higher in TA muscle, while the expression of Parkin (about 18.8% decreases，p＜0.05) and the ratio between LC3 II/I (about 26.0% decreases，p＜0.05)expression in SOL muscle were significantly lower. Conclusions In this study, we found that the percentage of fast muscle fibers was elevated in IR skeletal muscle, which were supported by increased Myhc4 and decreased Myhc7 level. Impaired mitochondrial function was only observed in slow muscle as inhibition of mitochondrial respiration. As marker of UPRmt, HSP60/70 were specifically activated in fast muscle in IR, while mitophagy-related proteins were specifically increased in slow muscle. These results indicate that mitochondrial quality control systems are selectively activated to recover mitochondrial functions depending on muscle fiber types in insulin resistant rat.

The influence of aerobic exercise on mitochondrial quality control in skeletal muscle

2021 ◽  
Author(s):  
Ashleigh M. Philp ◽  
Nicholas J. Saner ◽  
Michael Lazarou ◽  
Ian G. Ganley ◽  
Andrew Philp
Keyword(s):  
Skeletal Muscle ◽  
Quality Control ◽  
Aerobic Exercise ◽  
Mitochondrial Quality Control

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 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.

scholarly journals Trimetazidine and exercise provide comparable improvements to high fat diet-induced muscle dysfunction through enhancement of mitochondrial quality control

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wenliang Zhang ◽  
Baiyang You ◽  
Dake Qi ◽  
Ling Qiu ◽  
Jeffrey W. Ripley-Gonzalez ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Quality Control ◽  
Mitochondrial Dysfunction ◽  
Muscle Atrophy ◽  
High Fat Diet ◽  
C2c12 Cells ◽  
Muscle Dysfunction ◽  
High Fat ◽  
Mitochondrial Quality Control ◽  
Mitochondrial Functions

AbstractObesity induces skeletal muscle dysfunction. The pathogenesis of which appears to substantially involve mitochondrial dysfunction, arising from impaired quality control. Exercise is a major therapeutic strategy against muscle dysfunction. Trimetazidine, a partial inhibitor of lipid oxidation, has been proposed as a metabolic modulator for several cardiovascular pathologies. However, the effects of Trimetazidine on regulating skeletal muscle function are largely unknown. Our present study used cell culture and obese mice models to test a novel hypothesis that Trimetazidine could improve muscle atrophy with similar results to exercise. In C2C12 cells, high palmitic acid-induced atrophy and mitochondrial dysfunction, which could be reversed by the treatment of Trimetazidine. In our animal models, with high-fat diet-induced obesity associated with skeletal muscle atrophy, Trimetazidine prevented muscle dysfunction, corrected metabolic abnormalities, and improved mitochondrial quality control and mitochondrial functions similarly to exercise. Thus, our study suggests that Trimetazidine successfully mimics exercise to enhance mitochondrial quality control leading to improved high-fat diet-induced muscle dysfunction.

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