Mitochondrial Dynamics Is a Distinguishing Feature of Skeletal Muscle Fiber Types and Regulates Organellar Compartmentalization

Thyroid hormones (TH) are crucial for development, growth, differentiation, metabolism and thermogenesis. Skeletal muscle (SM) contractile function, myogenesis and bioenergetic metabolism are influenced by TH. These effects depend on the presence of the TH transporters MCT8 and MCT10 in the plasma membrane, the expression of TH receptors (THRA or THRB) and hormone availability, which is determined either by the activation of thyroxine (T 4 ) into triiodothyronine (T 3 ) by type 2 iodothyronine deiodinases (D2) or by the inactivation of T 4 into reverse T 3 by deiodinases type 3 (D3). SM relaxation and contraction rates depend on T 3 regulation of myosin expression and energy supplied by substrate oxidation in the mitochondria. The balance between D2 and D3 expression determines TH intracellular levels and thus influences the proliferation and differentiation of satellite cells, indicating an important role of TH in muscle repair and myogenesis. During critical illness, changes in TH levels and in THR and deiodinase expression negatively affect SM function and repair. This review will discuss the influence of TH action on SM contraction, bioenergetics metabolism, myogenesis and repair in health and illness conditions.

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“…As represented in Fig. 1, slowtwitch SM presents more mitochondria than fast-twitch ones (Mishra et al 2015).…”

Section: Thyroid Hormone Affects Skeletal Muscle Metabolismmentioning

confidence: 99%

Role of thyroid hormone in skeletal muscle physiology

Bloise

Cordeiro

Ortiga-Carvalho

2018

Journal of Endocrinology

146

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“…In skeletal muscle, scanning electron microscopy has shown that acute exercise results in increased structural interactions among mitochondria (29). In addition, elevated Mfn1 and Mfn2 mRNA levels (30), as well as increased mitochondrial continuity (20), have been observed after exercise. Finally, slow-twitch/oxidative fibers that are permanently stimulated by action potentials exhibit a higher frequency of fusion events than fast-twitch/glycolytic fibers that exhibit isolated acute trains of stimulation (20,31).…”

mentioning

confidence: 98%

“…In adult skeletal muscle fibers, the other form of striated muscle, we (17) and others (18)(19)(20) have recently demonstrated that mitochondria are dynamically connected and undergo frequent fusion events dependent on an outer mitochondrial membrane (OMM) fusion protein, mitofusin 1 (Mfn1), and the inner mitochondrial membrane Significance Mitochondrial function is supported by dynamic quality control processes, such as mitochondrial fusion. Cardiac contractility depends on mitochondrial metabolism, yet in cardiomyocytes, mitochondria are confined among myofibrils, raising questions about the possibility of mitochondrial physical communication.…”

mentioning

confidence: 99%

Mitochondrial fusion dynamics is robust in the heart and depends on calcium oscillations and contractile activity

Eisner

Cupo

Gao

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

138

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Mitochondrial fusion is thought to be important for supporting cardiac contractility, but is hardly detectable in cultured cardiomyocytes and is difficult to directly evaluate in the heart. We overcame this obstacle through in vivo adenoviral transduction with matrix-targeted photoactivatable GFP and confocal microscopy. Imaging in whole rat hearts indicated mitochondrial network formation and fusion activity in ventricular cardiomyocytes. Promptly after isolation, cardiomyocytes showed extensive mitochondrial connectivity and fusion, which decayed in culture (at 24-48 h). Fusion manifested both as rapid content mixing events between adjacent organelles and slower events between both neighboring and distant mitochondria. Loss of fusion in culture likely results from the decline in calcium oscillations/contractile activity and mitofusin 1 (Mfn1), because (i) verapamil suppressed both contraction and mitochondrial fusion, (ii) after spontaneous contraction or short-term field stimulation fusion activity increased in cardiomyocytes, and (iii) ryanodine receptor-2-mediated calcium oscillations increased fusion activity in HEK293 cells and complementing changes occurred in Mfn1. Weakened cardiac contractility in vivo in alcoholic animals is also associated with depressed mitochondrial fusion. Thus, attenuated mitochondrial fusion might contribute to the pathogenesis of cardiomyopathy.ardiac contractions require a constant energy supply, which is provided by mitochondrial metabolism. ATP is needed for excitation-contraction coupling (ECC) for both contraction and relaxation in each cycle (1, 2). ECC-associated cytoplasmic Ca 2+ transients ([Ca 2+ ] c ) are propagated to the mitochondrial matrix (3) to regulate Ca 2+ -dependent mitochondrial dehydrogenases, ATP synthesis, and intracellular Ca 2+ homeostasis (4). Thus, cardiac mitochondria are forced to work permanently and likely require quality control mechanisms to keep them in a functioning state.In many tissues, mitochondria are permanently rebuilt through evolutionarily conserved cyclic processes of fusion and fission. Fusion involves content exchange, allowing complementation of mitochondrial solutes, proteins, and DNA. Fission allows segregation of damaged components (5, 6). Both fusion and fission are promoted by mitochondrial movements that can bring distant mitochondria close to one another and can also separate interacting structures (7). However, the spatial arrangements and mitochondrial morphology are determined by sarcomers in ventricular myocytes, the contractile units of the adult mammalian heart. The gaps among densely packed parallel myofibrils are inhabited by bullet-like mitochondria that run longitudinally, interacting intimately with the junctional sarcoplasmic reticulum (SR), in a conformation that facilitates Ca 2+ exchange and supports ECC (4,8). Despite the spatial restrictions intrinsic to adult cardiomyocyte mitochondria, interactions among these organelles have been proposed based on functional observations. Reactive oxygen species (ROS)...

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“…This location allows mitochondria to communicate with one another via a complex network (100) and to participate in physiological functions by regulated fission and fusion mechanisms, termed "mitochondrial dynamics." Although little is known about mitochondrial dynamics in skeletal muscle, mitochondrial dynamics have been implicated in mitochondrial DNA renewal, cell differentiation and development, mitochondrial respiration, and bioenergetics (46,100,120,129,142).…”

Section: Basic Knowledge Of Myocytes: Importance Of Mitochondriamentioning

confidence: 99%

Chronology of mitochondrial and cellular events during skeletal muscle ischemia-reperfusion

Paradis

Charles

Meyer

et al. 2016

American Journal of Physiology-Cell Physiology

104

127

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Peripheral artery disease (PAD) is a common circulatory disorder of the lower limb arteries that reduces functional capacity and quality of life of patients. Despite relatively effective available treatments, PAD is a serious public health issue associated with significant morbidity and mortality. Ischemia-reperfusion (I/R) cycles during PAD are responsible for insufficient oxygen supply, mitochondriopathy, free radical production, and inflammation and lead to events that contribute to myocyte death and remote organ failure. However, the chronology of mitochondrial and cellular events during the ischemic period and at the moment of reperfusion in skeletal muscle fibers has been poorly reviewed. Thus, after a review of the basal myocyte state and normal mitochondrial biology, we discuss the physiopathology of ischemia and reperfusion at the mitochondrial and cellular levels. First we describe the chronology of the deleterious biochemical and mitochondrial mechanisms activated by I/R. Then we discuss skeletal muscle I/R injury in the muscle environment, mitochondrial dynamics, and inflammation. A better understanding of the chronology of the events underlying I/R will allow us to identify key factors in the development of this pathology and point to suitable new therapies. Emerging data on mitochondrial dynamics should help identify new molecular and therapeutic targets and develop protective strategies against PAD.peripheral artery disease; ischemia-reperfusion; skeletal muscle; mitochondria; oxidative stress PERIPHERAL ARTERY DISEASE (PAD) refers to a common circulatory disorder of the lower limb caused by chronic narrowing of the arteries (e.g., stenosis and occlusion) or atherosclerosis. PAD represents a broad spectrum of disease severity, ranging from asymptomatic disease to frequent pain when walking (i.e., intermittent claudication or limping) or critical limb ischemia associated with decubitus pain and/or ulcers (114,126).PAD is known to be associated with reduced functional capacity and quality of life. It is a major cause of limb amputation, as well as an increased risk factor for myocardial infarction, stroke, and death. The incidence of PAD varies with age, from 3-10% in young people to 15-20% in people Ͼ70 yr of age, and is asymptomatic in 40% of the cases (1), with greater prevalence among men. The major PAD risk factors, including smoking, diabetes mellitus, dyslipidemia, hypertension, and obesity, are the same as those for cardiovascular and cerebrovascular diseases (35).Three main complementary treatment options improve the functional status and other clinical outcomes in PAD patients (54). 1) Optimization of medical therapy (i.e., pharmacotherapy) reduces the risk of cardiac ischemia, increases the distance a patient can walk, and improves the functional capacity of patients. 2) When possible, exercise training, a noninvasive and nonpharmacological therapy, improves walking ability and has protective effects in patients with PAD characterized by intermittent claudication and infrainguinal lesions...

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Mitochondrial Dynamics Is a Distinguishing Feature of Skeletal Muscle Fiber Types and Regulates Organellar Compartmentalization

Cited by 225 publications

References 49 publications

Role of thyroid hormone in skeletal muscle physiology

Role of thyroid hormone in skeletal muscle physiology

Mitochondrial fusion dynamics is robust in the heart and depends on calcium oscillations and contractile activity

Chronology of mitochondrial and cellular events during skeletal muscle ischemia-reperfusion

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