Resistance Exercise Improves Mitochondrial Quality Control in a Rat Model of Sporadic Inclusion Body Myositis

Gerontology ◽  
2019 ◽  
Vol 65 (3) ◽  
pp. 240-252 ◽  
Author(s):  
Jung-Hoon Koo ◽  
Eun-Bum Kang ◽  
Joon-Yong Cho
Keyword(s):  
Quality Control ◽  
Rat Model ◽  
Mitochondrial Function ◽  
Inclusion Body Myositis ◽  
Oxidative Capacity ◽  
Control Group ◽  
Mitochondrial Quality Control ◽  
Mitochondrial Oxidative Capacity ◽  
Sporadic Inclusion Body Myositis ◽  
Muscle Impairment

Background: Mitochondrial dysfunction is implicated in the pathogenesis of multiple muscular diseases, including sporadic inclusion body myositis (s-IBM), the most common aging-related muscle disease. However, the factors causing mitochondrial dysfunction in s-IBM are unknown. Objective: We hypothesized that resistance exercise (RE) may alleviate muscle impairment by improving mitochondrial function via reducing amyloid-beta (Aβ) accumulation. Methods: Twenty-four male Wistar rats were randomized to a saline-injection control group (sham, n = 8), a chloroquine (CQ) control group (CQ-CON, n = 8), and a CQ plus RE group (CQ-RE, n = 8) in which rats climbed a ladder with weight attached to their tails 9 weeks after starting CQ treatment. Results: RE markedly inhibited soleus muscle atrophy and muscle damage. RE reduced CQ-induced Aβ accumulation, which resulted in decreased formation of rimmed vacuoles and mitochondrial-mediated apoptosis. Most importantly, the decreased Aβ accumulation improved both mitochondrial quality control (MQC) through increased mitochondrial biogenesis and mitophagy, and mitochondrial dynamics. Furthermore, RE-mediated reduction of Aβ accumulation elevated mitochondrial oxidative capacity by upregulating superoxide dismutase-2, catalase, and citrate synthase via activating sirtuin 3 signaling. Conclusion: RE enhances mitochondrial function by improving MQC and mitochondrial oxidative capacity via reducing Aβ accumulation, thereby inhibiting CQ-induced muscle impairment, in a rat model of s-IBM.

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.

Inclusion body myositis in patients with spinocerebellar ataxia types 3 and 6

2020 ◽  
Vol 91 (8) ◽  
pp. 876-878
Author(s):  
Anke Rietveld ◽  
Judith van Gaalen ◽  
Christiaan Saris ◽  
Kees Okkersen ◽  
Benno Küsters ◽  
...  
Keyword(s):  
Quality Control ◽  
Inclusion Body ◽  
Spinocerebellar Ataxia ◽  
Neurological Examination ◽  
Inclusion Body Myositis ◽  
Disease Mechanisms ◽  
Sporadic Inclusion Body Myositis ◽  
Type 3 ◽  
Muscle Ultrasound ◽  
Made In

ObjectivesTo describe the combination of spinocerebellar ataxia (SCA) types 3 and 6 and sporadic inclusion body myositis (IBM).MethodsA description of five patients with SCA type 3 and 6 who were diagnosed with IBM. We explore possible mechanisms explaining the coexistence of both diseases.ResultsThe patients with SCA-3 (n=4) and SCA-6 (n=1) developed asymmetric muscle weakness in a pattern suggestive of IBM in the course of their disease. Based on findings of neurological examination and additional investigations (muscle ultrasound, muscle biopsy), the diagnosis of IBM was made in all patients.ConclusionWe report on five patients with concomitant SCA and IBM. Our cases may merely illustrate coincidental co-occurrence of IBM and SCA-3/SCA-6. However, the presence of SCA mutations could predispose to the development of IBM in some SCA patients, or, the presence of toxic aggregates and malfunctioning of cellular quality control processes in both diseases could indicate a convergence of disease mechanisms.

Dystrophin deficiency disrupts muscle clock expression and mitochondrial quality control in mdx mice

2021 ◽  
Author(s):  
Justin P. Hardee ◽  
Marissa K. Caldow ◽  
Audrey S.M. Chan ◽  
Stuart K. Plenderleith ◽  
Jennifer Trieu ◽  
...  
Keyword(s):  
Quality Control ◽  
Mrna Expression ◽  
Tibialis Anterior ◽  
Oxidative Capacity ◽  
Mdx Mice ◽  
Dark Cycle ◽  
Mitochondrial Quality Control ◽  
The Core ◽  
Dystrophin Deficiency ◽  
Diurnal Regulation

Impaired oxidative capacity and mitochondrial function contribute to the dystrophic pathology in muscles of Duchenne muscular dystrophy (DMD) patients and in relevant mouse models of the disease. Emerging evidence suggests an association between disrupted core clock expression and mitochondrial quality control, but this has not been established in muscles lacking dystrophin. We examined the diurnal regulation of muscle core clock and mitochondrial quality control expression in dystrophin-deficient C57BL/10ScSn-Dmdmdx (mdx) mice, an established model of DMD. Male C57BL/10 (BL/10; n=18) and mdx mice (n=18) were examined every 4 hours beginning at the dark cycle. Throughout the entire light-dark cycle, extensor digitorum longus (EDL) muscles from mdx mice had decreased core clock mRNA expression (Arntl, Cry1, Cry2, Nr1d2; p<0.05) and disrupted mitochondrial quality control mRNA expression related to biogenesis (decreased; Ppargc1a, Esrra; p<0.05), fission (increased; Dnm1l; p<0.01), fusion (decreased; Opa1, Mfn1; p<0.05) and autophagy/mitophagy (decreased: Bnip3; p<0.05; increased: Becn1; p<0.05). Cosinor analysis revealed a decrease in the rhythmicity parameters mesor and amplitude for Arntl, Cry1, Cry2, Per2, and Nr1d1 (p<0.001) in mdx mice. Diurnal oscillations in Esrra, Sirt1, Map1lc3b and Sqstm1 were absent in mdx mice, along with decreased mesor and amplitude of Ppargc1a mRNA expression (p<0.01). The expression of proteins involved in mitochondrial biogenesis (decreased: PPARGC1A, p<0.05) and autophagy/mitophagy (increased: MAP1LC3BII, SQSTM1, BNIP3; p<0.05) were also dysregulated in tibialis anterior muscles of mdx mice. These findings suggest that dystrophin deficiency in mdx mice impairs the regulation of the core clock and mitochondrial quality control, with relevance to DMD and related disorders.

scholarly journals Tongyang Huoxue Decoction (TYHX) Ameliorating Hypoxia/Reoxygenation-Induced Disequilibrium of Calcium Homeostasis and Redox Imbalance via Regulating Mitochondrial Quality Control in Sinoatrial Node Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Xing Chang ◽  
Shunyu Yao ◽  
Qiaomin Wu ◽  
Yanli Wang ◽  
Jinfeng Liu ◽  
...  
Keyword(s):  
Quality Control ◽  
Calcium Homeostasis ◽  
Mitochondrial Function ◽  
Calcium Release ◽  
Sinoatrial Node ◽  
Redox Balance ◽  
Calcium Overload ◽  
Mitochondrial Quality Control ◽  
Redox Imbalance ◽  
Β Tubulin

Sick sinus syndrome (SSS) is a disease with bradycardia or arrhythmia. The pathological mechanism of SSS is mainly due to the abnormal conduction function of the sinoatrial node (SAN) caused by interstitial lesions or fibrosis of the SAN or surrounding tissues, SAN pacing dysfunction, and SAN impulse conduction accompanied by SAN fibrosis. Tongyang Huoxue Decoction (TYHX) is widely used in SSS treatment and amelioration of SAN fibrosis. It has a variety of active ingredients to regulate the redox balance and mitochondrial quality control. This study mainly discusses the mechanism of TYHX in ameliorating calcium homeostasis disorder and redox imbalance of sinoatrial node cells (SANCs) and clarifies the protective mechanism of TYHX on the activity of SANCs. The activity of SANCs was determined by CCK-8 and the TUNEL method. The levels of apoptosis, ROS, and calcium release were analyzed by flow cytometry and immunofluorescence. The mRNA and protein levels of calcium channel regulatory molecules and mitochondrial quality control-related molecules were detected by real-time quantitative PCR and Western Blot. The level of calcium release was detected by laser confocal. It was found that after H/R treatment, the viability of SANCs decreased significantly, the levels of apoptosis and ROS increased, and the cells showed calcium overload, redox imbalance, and mitochondrial dysfunction. After treatment with TYHX, the cell survival level was improved, calcium overload and oxidative stress were inhibited, and mitochondrial energy metabolism and mitochondrial function were restored. However, after the SANCs were treated with siRNA (si-β-tubulin), the regulation of TYHX on calcium homeostasis and redox balance was counteracted. These results suggest that β-tubulin interacts with the regulation of mitochondrial function and calcium release. TYHX may regulate mitochondrial quality control, maintain calcium homeostasis and redox balance, and protect SANCs through β-tubulin. The regulation mechanism of TYHX on mitochondrial quality control may also become a new target for SSS treatment.

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 Vanadium Induces Oxidative Stress and Mitochondrial Quality Control Disorder in the Heart of Ducks

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhiwei Xiong ◽  
Chenghong Xing ◽  
Tianfang Xu ◽  
Yan Yang ◽  
Guohui Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Quality Control ◽  
Mitochondrial Fission ◽  
Control Group ◽  
Mrna Levels ◽  
Mitochondrial Quality Control ◽  
Related Factors ◽  
Sod Activity ◽  
Vacuolar Degeneration ◽  
Mitochondrial Functions

Vanadium (V) is an ultra-trace element presenting in humans and animals, but excessive V can cause toxic effects. Mitochondrial quality control (MQC) is an essential process for maintaining mitochondrial functions, but the relationship between V toxicity and MQC is unclear. To investigate the effects of excessive V on oxidative stress and MQC in duck hearts, 72 ducks were randomly divided into two groups, including the control group and the V group (30 mg of V/kg dry matter). The cardiac tissues were collected for the histomorphology observation and oxidative stress status evaluation at 22 and 44 days. In addition, the mRNA and protein levels of MQC-related factors were also analyzed. The results showed that excessive V could trigger vacuolar degeneration, granular degeneration, as well as mitochondrial vacuolization and swelling in myocardial cells. In addition, CAT activity was elevated in two time points, while T-SOD activity was increased in 22 days but decreased in 44 days after V treatment. Meanwhile, excessive V intake could also increase the number of Drp1 puncta, the mRNA levels of mitochondrial fission–related factors (Drp1and MFF), and protein (MFF) level, but decrease the number of Parkin puncta and the mitochondrial biogenesis (PGC-1α, NRF-1, and TFAM), mitochondrial fusion (OPA1, Mfn1, and Mfn2), and mitophagy (Parkin, PINK1, P62, and LC3B) related mRNA levels and protein (PGC-1α, Mfn1, Mfn2, PINK1) levels. Collectively, our results suggested that excessive V could induce oxidative stress and MQC disorder in the heart of ducks.

scholarly journals Increased Trimethylamine N-oxide Contributes to Metabolic dysfunction in a Rat Model of PCOS and Decreases Mitochondrial function

2020 ◽  
Author(s):  
Huang Jiayu ◽  
Liu Jiaying ◽  
Zhang Hanke ◽  
Li Yajie ◽  
Minuo Yin ◽  
...  
Keyword(s):  
Rat Model ◽  
Mitochondrial Function ◽  
Group Treatment ◽  
Intestinal Flora ◽  
Control Group ◽  
Metabolic Dysfunction ◽  
Childbearing Age ◽  
The Relationship

Abstract Polycystic ovarian syndrome (PCOS) is a common endocrine disease in adolescents and women of childbearing age, also a common cause of female infertility. In recent years, studies have found that the occurrence of PCOS is related to changes in the intestinal flora. Trimethylamine N-oxide (TMAO) is an organic compound produced by intestinal microorganisms. However, the relationship between TMAO and PCOS remain mostly unexplored. The effects of TMAO on PCOS were assessed in vitro and in vivo. In a PCOS rat model, plasma TMAO, hormone and PI3K signaling levels were examined. In the process of in vitro maturation (IVM), immunofluorescence and confocal microscopy were used to detect the influence of adding different TMAO concentrations to the culture medium on oocytes. The fasting insulin (FINS), HOMA-IR, luteinizing hormone (LH), LH/follicle-stimulating hormone (FSH) and plasma TMAO levels of the PCOS rat group were significantly higher than those of the control group. Treatment with the TMAO inhibitor 3,3-dimethyl-1-butanol (DMB) alleviated metabolic disorder in PCOS rats. In PCOS rats, DMB improved the PI3K/Akt-related signaling pathway compared to no treatment. In IVM, the mitochondria of oocytes in the TMAO groups were aggregated and distributed, and mitochondrial membrane potential and ATP content were decreased. Apoptosis was more severe in the TMAO group than in the control group. TMAO worsened metabolic dysfunction in a rat model of PCOS and decreased the mitochondrial function of oocytes in the process of IVM.

scholarly journals Empagliflozin attenuates diabetic tubulopathy by improving mitochondrial fragmentation and autophagy

2019 ◽  
Vol 317 (4) ◽  
pp. F767-F780 ◽  
Author(s):  
Yu Ho Lee ◽  
Sang Hoon Kim ◽  
Jun Mo Kang ◽  
Jin Hyung Heo ◽  
Dong-Jin Kim ◽  
...  
Keyword(s):  
Quality Control ◽  
Protein Expression ◽  
High Glucose ◽  
Mitochondrial Dynamics ◽  
Control Group ◽  
Mitochondrial Fragmentation ◽  
Mitochondrial Quality Control ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Renal Tubular

We examined the effects of empagliflozin, a selective inhibitor of Na+-glucose cotransporter 2, on mitochondrial quality control and autophagy in renal tubular cells in a diabetic environment in vivo and in vitro. Human renal proximal tubular cells (hRPTCs) were incubated under high-glucose conditions. Diabetes was induced with streptozotocin in male C57BL/6J mice. Improvements in mitochondrial biogenesis and balanced fusion-fission protein expression were noted in hRPTCs after treatment with empagliflozin in high-glucose media. Empagliflozin also increased autophagic activities in renal tubular cells in the high-glucose environment, which was accompanied with mammalian target of rapamycin inhibition. Moreover, reduced mitochondrial reactive oxygen species production and decreased apoptotic and fibrotic protein expression were observed in hRPTCs after treatment with empagliflozin, even in the hyperglycemic circumstance. Importantly, empagliflozin restored AMP-activated protein kinase-α phosphorylation and normalized levels of AMP-to-ATP ratios in hRPTCs subjected to a high-glucose environment, which suggests the way that empagliflozin is involved in mitochondrial quality control. Empagliflozin effectively suppressed Na+-glucose cotransporter 2 expression and ameliorated renal morphological changes in the kidneys of streptozotocin-induced diabetic mice. Electron microscopy analysis showed that mitochondrial fragmentation was decreased and 8-hydroxy-2′-deoxyguanosine content was low in renal tubular cells of empagliflozin treatment groups compared with those of the diabetic control group. We suggest one mechanism related to the renoprotective actions of empagliflozin, which reverse mitochondrial dynamics and autophagy.

scholarly journals Elevated Lactate by High-Intensity Interval Training Regulates the Hippocampal BDNF Expression and the Mitochondrial Quality Control System

2021 ◽  
Vol 12 ◽  
Author(s):  
Jingyun Hu ◽  
Ming Cai ◽  
Qinghui Shang ◽  
Zhaorun Li ◽  
Yu Feng ◽  
...  
Keyword(s):  
Quality Control ◽  
Control System ◽  
Mitochondrial Function ◽  
Interval Training ◽  
Quality Control System ◽  
Bdnf Expression ◽  
Mitochondrial Quality Control ◽  
High Intensity Interval

High-intensity interval training (HIIT) is reported to be beneficial to brain-derived neurotrophic factor (BDNF) biosynthesis. A key element in this may be the existence of lactate, the most obvious metabolic product of exercise. In vivo, this study investigated the effects of a 6-week HIIT on the peripheral and central lactate changes, mitochondrial quality control system, mitochondrial function and BDNF expression in mouse hippocampus. In vitro, primary cultured mice hippocampal cells were used to investigate the role and the underlying mechanisms of lactate in promoting mitochondrial function during HIIT. In vivo studies, we firstly reported that HIIT can potentiate mitochondrial function [boost some of the mitochondrial oxidative phosphorylation (OXPHOS) genes expression and ATP production], stimulate BDNF expression in mouse hippocampus along with regulating the mitochondrial quality control system in terms of promoting mitochondrial fusion and biogenesis, and suppressing mitochondrial fission. In parallel to this, the peripheral and central lactate levels elevated immediately after the training. In vitro study, our results revealed that lactate was in charge of regulating mitochondrial quality control system for mitochondrial function and thus may contribute to BDNF expression. In conclusion, our study provided the mitochondrial mechanisms of HIIT enhancing brain function, and that lactate itself can mediate the HIIT effect on mitochondrial quality control system in the hippocampus.

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