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Scandinavian Journal of Medicine &... Dec 2015The importance of glycogen, as a fuel during exercise, is a fundamental concept in exercise physiology. The use of electron microscopy has revealed that glycogen is not... (Review)
Review
The importance of glycogen, as a fuel during exercise, is a fundamental concept in exercise physiology. The use of electron microscopy has revealed that glycogen is not evenly distributed in skeletal muscle fibers, but rather localized in distinct pools. In this review, we present the available evidence regarding the subcellular localization of glycogen in skeletal muscle and discuss this from the perspective of skeletal muscle fiber function. The distribution of glycogen in the defined pools within the skeletal muscle varies depending on exercise intensity, fiber phenotype, training status, and immobilization. Furthermore, these defined pools may serve specific functions in the cell. Specifically, reduced levels of these pools of glycogen are associated with reduced SR Ca(2+) release, muscle relaxation rate, and membrane excitability. Collectively, the available literature strongly demonstrates that the subcellular localization of glycogen has to be considered to fully understand the role of glycogen metabolism and signaling in skeletal muscle function. Here, we propose that the effect of low muscle glycogen on excitation-contraction coupling may serve as a built-in mechanism, which links the energetic state of the muscle fiber to energy utilization.
Topics: Animals; Calcium; Cell Plasticity; Excitation Contraction Coupling; Exercise; Glycogen; Humans; Muscle Fibers, Skeletal; Myofibrils; Sarcoplasmic Reticulum; Sarcoplasmic Reticulum Calcium-Transporting ATPases
PubMed: 26589115
DOI: 10.1111/sms.12599 -
Recent Advances in DNA & Gene Sequences 2015Skeletal muscle represents one of the most plastic tissues of our body thanks to the presence of heterogeneous population of myofibers that confer to skeletal muscle the... (Review)
Review
Skeletal muscle represents one of the most plastic tissues of our body thanks to the presence of heterogeneous population of myofibers that confer to skeletal muscle the functional plasticity necessary to modulate its morpho-fuctional properties in response to a wide range of external factors. Thus, alteration in fiber type composition represents a major component in muscle wasting associated with muscle diseases. Several mechanisms have been proposed to account for the alteration in the morpho-functional properties of skeletal muscle under pathological conditions. In this review we will discuss the potential catabolic mediators of muscle atrophy and wasting.
Topics: Cachexia; Humans; Muscle, Skeletal; Muscular Atrophy; Myofibrils; Proteolysis; Signal Transduction
PubMed: 26361781
DOI: 10.2174/2352092209999150911121502 -
Journal of Biomechanics Sep 2021Sarcomere length non-uniformities occur at all structural levels of skeletal muscles and have been associated with important mechanical properties. Changes in sarcomere...
Sarcomere length non-uniformities occur at all structural levels of skeletal muscles and have been associated with important mechanical properties. Changes in sarcomere length non-uniformities in the nano- and sub-nanometer range have been used to explain muscle properties and contractile mechanisms. Typically, these measurements rely on light microscopy with a limited spatial resolution. One critical aspect in sarcomere length determination is the relatively arbitrary choice of intensity thresholds used to delineate sarcomere structures, such as A-bands or Z-lines. In experiments, these structures are typically distorted, intensity profiles vary, and baselines drift, resulting in asymmetric intensity patterns, causing changes in the centroid location of these structures depending on threshold choice, resulting in changes of sarcomere lengths. The purpose of this study was to determine the changes in (half-) sarcomere lengths associated with small changes in the A-band threshold choice. Sarcomere and half-sarcomere length changes for minute variations in A-band threshold were 28 nm (±28 nm) and 18 nm (±22 nm), respectively, and for the entire feasible range of thresholds across A-bands were 123 nm (±88 nm) and 99 nm (±105 nm), respectively. We conclude from these results that (half-) sarcomere lengths in the nanometer range obtained with light microcopy are noise, and the functional implications associated with such data should be discarded. We suggest that a functional resolution for sarcomere length of 100 nm (0.1 µm) is reasonable and 50 nm (0.05 µm) might be possible under ideal conditions.
Topics: Muscle Contraction; Muscle, Skeletal; Myofibrils; Reproducibility of Results; Sarcomeres
PubMed: 34274869
DOI: 10.1016/j.jbiomech.2021.110628 -
Nature Communications Apr 2021Complex animals build specialised muscles to match specific biomechanical and energetic needs. Hence, composition and architecture of sarcomeres and mitochondria are...
Complex animals build specialised muscles to match specific biomechanical and energetic needs. Hence, composition and architecture of sarcomeres and mitochondria are muscle type specific. However, mechanisms coordinating mitochondria with sarcomere morphogenesis are elusive. Here we use Drosophila muscles to demonstrate that myofibril and mitochondria morphogenesis are intimately linked. In flight muscles, the muscle selector spalt instructs mitochondria to intercalate between myofibrils, which in turn mechanically constrain mitochondria into elongated shapes. Conversely in cross-striated leg muscles, mitochondria networks surround myofibril bundles, contacting myofibrils only with thin extensions. To investigate the mechanism causing these differences, we manipulated mitochondrial dynamics and found that increased mitochondrial fusion during myofibril assembly prevents mitochondrial intercalation in flight muscles. Strikingly, this causes the expression of cross-striated muscle specific sarcomeric proteins. Consequently, flight muscle myofibrils convert towards a partially cross-striated architecture. Together, these data suggest a biomechanical feedback mechanism downstream of spalt synchronizing mitochondria with myofibril morphogenesis.
Topics: Animals; Biomechanical Phenomena; Drosophila; Drosophila Proteins; Drosophila melanogaster; Feedback; Flight, Animal; Male; Mechanical Phenomena; Mitochondria; Morphogenesis; Muscle Development; Muscle, Skeletal; Myofibrils; Myogenic Regulatory Factors; Sarcomeres; Transcription Factors
PubMed: 33828099
DOI: 10.1038/s41467-021-22058-7 -
Theranostics 2021Bio-engineered myocardium has great potential to substitute damaged myocardium and for studies of myocardial physiology and disease, but structural and functional...
Bio-engineered myocardium has great potential to substitute damaged myocardium and for studies of myocardial physiology and disease, but structural and functional immaturity still implies limitations. Current protocols of engineered heart tissue (EHT) generation fall short of simulating the conditions of postnatal myocardial growth, which are characterized by tissue expansion and increased mechanical load. To investigate whether these two parameters can improve EHT maturation, we developed a new approach for the generation of cardiac tissues based on biomimetic stimulation under application of continuously increasing stretch. EHTs were generated by assembling cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CM) at high cell density in a low collagen hydrogel. Maturation and growth of the EHTs were induced in a custom-made biomimetic tissue culture system that provided continuous electrical stimulation and medium agitation along with progressive stretch at four different increments. Tissues were characterized after a three week conditioning period. The highest rate of stretch (S3 = 0.32 mm/day) increased force development by 5.1-fold compared to tissue with a fixed length, reaching contractility of 11.28 mN/mm². Importantly, intensely stretched EHTs developed physiological length-dependencies of active and passive forces (systolic/diastolic ratio = 9.47 ± 0.84), and a positive force-frequency relationship (1.25-fold contractility at 180 min). Functional markers of stretch-dependent maturation included enhanced and more rapid Ca transients, higher amplitude and upstroke velocity of action potentials, and pronounced adrenergic responses. Stretch conditioned hiPSC-CMs displayed structural improvements in cellular volume, linear alignment, and sarcomere length (2.19 ± 0.1 µm), and an overall upregulation of genes that are specifically expressed in adult cardiomyocytes. With the intention to simulate postnatal heart development, we have established techniques of tissue assembly and biomimetic culture that avoid tissue shrinkage and yield muscle fibers with contractility and compliance approaching the properties of adult myocardium. This study demonstrates that cultivation under progressive stretch is a feasible way to induce growth and maturation of stem cell-derived myocardium. The novel tissue-engineering approach fulfills important requirements of disease modelling and therapeutic tissue replacement.
Topics: Biomimetic Materials; Bioreactors; Cell Size; Diastole; Electric Stimulation; Excitation Contraction Coupling; Humans; Hydrogels; Induced Pluripotent Stem Cells; Muscle Spindles; Myocardium; Myocytes, Cardiac; Myofibrils; Organoids; RNA, Messenger; Stress, Mechanical; Systole; Tissue Culture Techniques; Tissue Engineering
PubMed: 33995650
DOI: 10.7150/thno.54999 -
American Journal of Physiology. Cell... Aug 2017Muscle contraction is commonly associated with the cross-bridge and sliding filament theories, which have received strong support from experiments conducted over the... (Review)
Review
Muscle contraction is commonly associated with the cross-bridge and sliding filament theories, which have received strong support from experiments conducted over the years in different laboratories. However, there are studies that cannot be readily explained by the theories, showing ) a plateau of the force-length relation extended beyond optimal filament overlap, and forces produced at long sarcomere lengths that are higher than those predicted by the sliding filament theory; ) passive forces at long sarcomere lengths that can be modulated by activation and Ca, which changes the force-length relation; and ) an unexplained high force produced during and after stretch of activated muscle fibers. Some of these studies even propose "new theories of contraction." While some of these observations deserve evaluation, many of these studies present data that lack a rigorous control and experiments that cannot be repeated in other laboratories. This article reviews these issues, looking into studies that have used intact and permeabilized fibers, myofibrils, isolated sarcomeres, and half-sarcomeres. A common mechanism associated with sarcomere and half-sarcomere length nonuniformities and a Ca-induced increase in the stiffness of titin is proposed to explain observations that derive from these studies.
Topics: Animals; Biomechanical Phenomena; Calcium; Connectin; Isometric Contraction; Muscle Contraction; Muscle Fibers, Skeletal; Muscle, Striated; Myofibrils; Sarcomeres
PubMed: 28539306
DOI: 10.1152/ajpcell.00050.2017 -
Cells Nov 2021Nesprin-1 is a large scaffold protein connecting nuclei to the actin cytoskeleton via its KASH and Calponin Homology domains, respectively. Nesprin-1 disconnection from...
Nesprin-1 is a large scaffold protein connecting nuclei to the actin cytoskeleton via its KASH and Calponin Homology domains, respectively. Nesprin-1 disconnection from nuclei results in altered muscle function and myonuclei mispositioning. Furthermore, Nesprin-1 mutations are associated with muscular pathologies such as Emery Dreifuss muscular dystrophy and arthrogryposis. Nesprin-1 was thus proposed to mainly contribute to muscle function by controlling nuclei position. However, Nesprin-1's localisation at sarcomere's Z-discs, its involvement in organelles' subcellular localization, as well as the description of numerous isoforms presenting different combinations of Calponin Homology (CH) and KASH domains, suggest that the contribution of Nesprin-1 to muscle functions is more complex. Here, we investigate the roles of Nesprin-1/Msp300 isoforms in muscle function and subcellular organisation using larvae as a model. Subsets of Msp300 isoform were down-regulated by muscle-specific RNAi expression and muscle global function and morphology were assessed. We show that nuclei anchoring in mature muscle and global muscle function are disconnected functions associated with different Msp300 isoforms. Our work further uncovers a new and unsuspected role of Msp300 in myofibril registration and nuclei peripheral displacement supported by Msp300 CH containing isoforms, a function performed by Desmin in mammals.
Topics: Animals; Cell Nucleus; Drosophila Proteins; Drosophila melanogaster; Larva; Locomotion; Microfilament Proteins; Muscle Proteins; Muscles; Myofibrils; Phenotype; Protein Isoforms; RNA Interference
PubMed: 34831284
DOI: 10.3390/cells10113061 -
Cytoskeleton (Hoboken, N.J.) Oct 2020De novo assembly of myofibrils in vertebrate cross-striated muscles progresses in three distinct steps, first from a minisarcomeric alignment of several nonmuscle and...
De novo assembly of myofibrils in vertebrate cross-striated muscles progresses in three distinct steps, first from a minisarcomeric alignment of several nonmuscle and muscle proteins in premyofibrils, followed by insertions of additional proteins and increased organization in nascent myofibrils, ending with mature contractile myofibrils. In a search for controls of the process of myofibril assembly, we discovered that the transition from nascent to mature myofibrils could be halted by inhibitors of three distinct functions of the ubiquitin proteasome system (UPS). First, inhibition of pathway to E3 Cullin ligases that ubiquitinate proteins led to an arrest of myofibrillogenesis at the nascent myofibril stage. Second, inhibition of p97 protein extractions of ubiquitinated proteins led to a similar arrest of myofibrillogenesis at the nascent myofibril stage. Third, inhibitors of proteolytic action by proteasomes also blocked nascent myofibrils from transitioning to mature myofibrils. In contrast, inhibitors of autophagy or lysosomes did not affect myofibrillogenesis. To probe for differences in the effects of UPS inhibitors during myofibrillogenesis, we analyzed by fluorescence recovery after photobleaching the exchange rates of two selected sarcomeric proteins (muscle myosin II heavy chains and light chains). In the presence of p97 and proteasomal inhibitors, the dynamics of each of these two myosin proteins decreased in the nascent myofibril stage, but were unaffected in the mature myofibril stage. The increased stability of myofibrils occurring in the transition from nascent to mature myofibril assembly indicates the importance of dynamics and selective destruction in the muscle myosin II proteins for the remodeling of nascent to mature myofibrils.
Topics: Animals; Muscle, Skeletal; Myofibrils; Proteasome Endopeptidase Complex; Quail; Ubiquitin
PubMed: 33124174
DOI: 10.1002/cm.21641 -
Archives of Biochemistry and Biophysics Mar 2019
Review
Topics: Animals; Muscle Contraction; Muscle, Striated; Myofibrils
PubMed: 30639328
DOI: 10.1016/j.abb.2019.01.008 -
The Journal of General Physiology Jul 2021The July 2021 issue of is a collection of peer-reviewed articles focused on the function and dynamic regulation of contractile systems in muscle and non-muscle cells.
The July 2021 issue of is a collection of peer-reviewed articles focused on the function and dynamic regulation of contractile systems in muscle and non-muscle cells.
Topics: Myofibrils
PubMed: 34170286
DOI: 10.1085/jgp.202112972