bims-misrem Biomed News
on Mitochondria and sarcoplasmic reticulum in muscle mass
Issue of 2020‒05‒03
sixteen papers selected by
Rafael Antonio Casuso Pérez
University of Granada

  1. Diabetologia. 2020 Apr 29.
    Georgiadou E, Haythorne E, Dickerson MT, Lopez-Noriega L, Pullen TJ, da Silva Xavier G, Davis SPX, Martinez-Sanchez A, Semplici F, Rizzuto R, McGinty JA, French PM, Cane MC, Jacobson DA, Leclerc I, Rutter GA.
      AIMS/HYPOTHESIS: Mitochondrial oxidative metabolism is central to glucose-stimulated insulin secretion (GSIS). Whether Ca2+ uptake into pancreatic beta cell mitochondria potentiates or antagonises this process is still a matter of debate. Although the mitochondrial Ca2+ importer (MCU) complex is thought to represent the main route for Ca2+ transport across the inner mitochondrial membrane, its role in beta cells has not previously been examined in vivo.METHODS: Here, we inactivated the pore-forming subunit of the MCU, encoded by Mcu, selectively in mouse beta cells using Ins1Cre-mediated recombination. Whole or dissociated pancreatic islets were isolated and used for live beta cell fluorescence imaging of cytosolic or mitochondrial Ca2+ concentration and ATP production in response to increasing glucose concentrations. Electrophysiological recordings were also performed on whole islets. Serum and blood samples were collected to examine oral and i.p. glucose tolerance.
    RESULTS: Glucose-stimulated mitochondrial Ca2+ accumulation (p< 0.05), ATP production (p< 0.05) and insulin secretion (p< 0.01) were strongly inhibited in beta cell-specific Mcu-null (βMcu-KO) animals, in vitro, as compared with wild-type (WT) mice. Interestingly, cytosolic Ca2+ concentrations increased (p< 0.001), whereas mitochondrial membrane depolarisation improved in βMcu-KO animals. βMcu-KO mice displayed impaired in vivo insulin secretion at 5 min (p< 0.001) but not 15 min post-i.p. injection of glucose, whilst the opposite phenomenon was observed following an oral gavage at 5 min. Unexpectedly, glucose tolerance was improved (p< 0.05) in young βMcu-KO (<12 weeks), but not in older animals vs WT mice.
    CONCLUSIONS/INTERPRETATION: MCU is crucial for mitochondrial Ca2+ uptake in pancreatic beta cells and is required for normal GSIS. The apparent compensatory mechanisms that maintain glucose tolerance in βMcu-KO mice remain to be established.
    Keywords:  Calcium; Glucose homeostasis; Insulin secretion; Mitochondria; Mitochondrial Ca2+ uniporter (MCU); Pancreatic beta cells; Type 2 diabetes
  2. IUBMB Life. 2020 Apr 30.
    Zhou H, Yuan D, Gao W, Tian J, Sun H, Yu S, Wang J, Sun L.
      Cellular homeostasis requires tight coordination between nucleus and mitochondria, organelles that each possesses their own genomes. Disrupted mitonuclear communication has been found to be implicated in many aging processes. However, little is known about mitonuclear signaling regulator in sarcopenia which is a major contributor to the risk of poor health-related quality of life, disability, and premature death in older people. High-temperature requirement protein A2 (HtrA2/Omi) is a mitochondrial protease and plays an important role in mitochondrial proteostasis. HtrA2mnd2(-/-) mice harboring protease-deficient HtrA2/Omi Ser276Cys missense mutants exhibit premature aging phenotype. Additionally, HtrA2/Omi has been established as a signaling regulator in nervous system and tumors. We therefore asked whether HtrA2/Omi participates in mitonuclear signaling regulation in muscle degeneration. Using motor functional, histological, and molecular biological methods, we characterized the phenotype of HtrA2mnd2(-/-) muscle. Furthermore, we isolated the gastrocnemius muscle of HtrA2mnd2(-/-) mice and determined expression of genes in mitochondrial unfolded protein response (UPRmt ), mitohormesis, electron transport chain (ETC), and mitochondrial biogenesis. Here, we showed that HtrA2/Omi protease deficiency induced denervation-independent skeletal muscle degeneration with sarcopenia phenotypes. Despite mitochondrial hypofunction, upregulation of UPRmt and mitohormesis-related genes and elevated total reactive oxygen species (ROS) production were not observed in HtrA2mnd2(-/-) mice, contrary to previous assumptions that loss of protease activity of HtrA2/Omi would lead to mitochondrial dysfunction as a result of proteostasis disturbance and ROS burst. Instead, we showed that HtrA2/Omi protease deficiency results in different changes between the expression of nuclear DNA- and mitochondrial DNA-encoded ETC subunits, which is in consistent with their transcription factors, nuclear respiratory factors 1 and 2, and coactivator peroxisome proliferator-activated receptor γ coactivator 1α. These results reveal that loss of HtrA2/Omi protease activity induces mitonuclear imbalance via differential regulation of mitochondrial biogenesis in sarcopenia. The novel mechanistic insights may be of importance in developing new therapeutic strategies for sarcopenia.
    Keywords:  HtrA2/Omi; UPRmt; mitochondrial biogenesis; mitohormesis; mitonuclear imbalance; sarcopenia
  3. Antioxidants (Basel). 2020 Apr 23. pii: E345. [Epub ahead of print]9(4):
    Borja-Gonzalez M, Casas-Martinez JC, McDonagh B, Goljanek-Whysall K.
      Ageing is associated with disrupted redox signalling and increased circulating inflammatory cytokines. Skeletal muscle homeostasis depends on the balance between muscle hypertrophy, atrophy and regeneration, however during ageing this balance is disrupted. The molecular pathways underlying the age-related decline in muscle regenerative potential remain elusive. microRNAs are conserved robust gene expression regulators in all tissues including skeletal muscle. Here, we studied satellite cells from adult and old mice to demonstrate that inhibition of miR-21 in satellite cells from old mice improves myogenesis. We determined that increased levels of proinflammatory cytokines, TNFα and IL6, as well as H2O2, increased miR-21 expression in primary myoblasts, which in turn resulted in their decreased viability and myogenic potential. Inhibition of miR-21 function rescued the decreased size of myotubes following TNFα or IL6 treatment. Moreover, we demonstrated that miR-21 could inhibit myogenesis in vitro via regulating IL6R, PTEN and FOXO3 signalling. In summary, upregulation of miR-21 in satellite cells and muscle during ageing may occur in response to elevated levels of TNFα and IL6, within satellite cells or myofibrillar environment contributing to skeletal muscle ageing and potentially a disease-related decline in potential for muscle regeneration.
    Keywords:  IL6; IL6R; aging; cachexia; miR-21; microRNA; muscle; regeneration; sarcopenia
  4. Adv Exp Med Biol. 2020 ;1228 63-76
    Fan Z, Xu M.
      Chronic heart failure, diabetes, depression, and other chronic diseases are associated with high mortality rate and low cure rate. Exercise induces muscle contraction and secretes multiple myokines, which affects the signaling pathways in skeletal muscle tissues and regulate remote organ functions. Exercise is known to be effective in treating a variety of chronic diseases. Here we summarize how exercise influences skeletal muscle, heart, brain, gut, and liver, and prevents heart failure, cognitive dysfunction, obesity, fatty liver, and other diseases. Exercise training may achieve additional benefits as compared to the present medication for these chronic diseases through cross talk among skeletal muscle and other organs.
    Keywords:  Cross talk; Exercise; Myokines; Skeletal muscle
  5. Science. 2020 May 01. pii: eaat3987. [Epub ahead of print]368(6490):
    Knudsen NH, Stanya KJ, Hyde AL, Chalom MM, Alexander RK, Liou YH, Starost KA, Gangl MR, Jacobi D, Liu S, Sopariwala DH, Fonseca-Pereira D, Li J, Hu FB, Garrett WS, Narkar VA, Ortlund EA, Kim JH, Paton CM, Cooper JA, Lee CH.
      Repeated bouts of exercise condition muscle mitochondria to meet increased energy demand-an adaptive response associated with improved metabolic fitness. We found that the type 2 cytokine interleukin-13 (IL-13) is induced in exercising muscle, where it orchestrates metabolic reprogramming that preserves glycogen in favor of fatty acid oxidation and mitochondrial respiration. Exercise training-mediated mitochondrial biogenesis, running endurance, and beneficial glycemic effects were lost in Il13-/- mice. By contrast, enhanced muscle IL-13 signaling was sufficient to increase running distance, glucose tolerance, and mitochondrial activity similar to the effects of exercise training. In muscle, IL-13 acts through both its receptor IL-13Rα1 and the transcription factor Stat3. The genetic ablation of either of these downstream effectors reduced running capacity in mice. Thus, coordinated immunological and physiological responses mediate exercise-elicited metabolic adaptations that maximize muscle fuel economy.
  6. J Appl Physiol (1985). 2020 Apr 30.
    Kim K, Monroe JC, Gavin TP, Roseguini BT.
      The therapeutic effects of heat have been harnessed for centuries to treat skeletal muscle disorders and other pathologies. However, the fundamental mechanisms underlying the well-documented clinical benefits associated with heat therapy (HT) remain poorly defined. Foundational studies in cultured skeletal muscle and endothelial cells as well as in rodents revealed that episodic exposure to heat stress activates a number of intracellular signaling networks and promotes skeletal muscle remodeling. Renewed interest in the physiology of HT in recent years has provided greater understanding of the signals and molecular players involved in the skeletal muscle adaptations to episodic exposures to HT. It is increasingly clear that heat stress promotes signaling mechanisms involved in angiogenesis, muscle hypertrophy, mitochondrial biogenesis and glucose metabolism through not only elevations in tissue temperature but also other perturbations including increased intramyocellular calcium and enhanced energy turnover. The few available translational studies seem to indicate that the earlier observations in rodents also apply to human skeletal muscle. Indeed, recent findings revealed that both local and whole-body HT may promote capillary growth, enhance mitochondrial content and function, improve insulin sensitivity and attenuate disuse-induced muscle wasting. This accumulating body of work implies that HT may be a practical treatment to combat skeletal abnormalities in individuals with chronic disease who are unwilling or cannot participate in traditional exercise training regimens.
    Keywords:  heat therapy; skeletal muscle
  7. Am J Physiol Cell Physiol. 2020 Apr 29.
    Teigen LE, Sundberg CW, Kelly LJ, Hunter SK, Fitts RH.
      Age-induced declines in skeletal muscle contractile function have been attributed to multiple cellular factors, including lower peak force (Po), decreased Ca2+ sensitivity, and reduced shortening velocity (Vo). However, changes in these cellular properties with aging remain unresolved, especially in older women, and the effect of submaximal Ca2+ on contractile function is unknown. Thus, we compared contractile properties of muscle fibers from 19 young (24±3 years; 8 women) and 21 older adults (77±7 years; 7 women) under maximal and submaximal Ca2+ and assessed the abundance of three proteins thought to influence Ca2+ sensitivity. Fast fiber cross-sectional area was ~44% larger in young (6,479±2,487 µm2) compared to older adults (4,503±2,071 µm2, P<0.001), which corresponded with a greater absolute Po (young = 1.12±0.43 mN, old = 0.79±0.33 mN, P<0.001). There were no differences in fast fiber size-specific Po, indicating the age-related decline in force was explained by differences in fiber size. Except for fast fiber size and absolute Po, no age or sex differences were observed in Ca2+ sensitivity, rate of force development (ktr), or Vo in either slow or fast fibers. Submaximal Ca2+ depressed ktr and Vo, but the effects were not altered by age in either sex. Contrary to rodent studies, regulatory light chain (RLC) and myosin binding protein-C abundance and RLC phosphorylation were unaltered by age or sex. These data suggest the age-associated reductions in contractile function are primarily due to the atrophy of fast fibers and that caution is warranted when extending results from rodent studies to humans.
    Keywords:  aging; calcium; contractile properties; skeletal muscle fibers
  8. J Physiol. 2020 May 02.
    Glancy B, Kane DA, Kavazis AN, Goodwin ML, Willis WT, Gladden LB.
      Mitochondrial structures were probably observed microscopically in the 1840s, but the idea of oxidative phosphorylation (OXPHOS) within mitochondria did not appear until the 1930s. The foundation for research into energetics arose from Meyerhof's experiments on oxidation of lactate in isolated muscles recovering from electrical contractions in an O2 atmosphere. Today, we know that mitochondria are actually reticula and that the energy released from electron pairs being passed along the electron transport chain from NADH to O2 generates a membrane potential and pH gradient of protons that can enter the molecular machine of ATP Synthase to resynthesize ATP. Lactate stands at the crossroads of glycolytic and oxidative energy metabolism. Based on reported research and our own modeling in silico, we contend that lactate is not directly oxidized in the mitochondrial matrix. Instead, the interim glycolytic products (pyruvate and NADH) are held in cytosolic equilibrium with the products of the lactate dehydrogenase (LDH) reaction and the intermediates of the malate-aspartate and glycerol 3-phosphate shuttles. This equilibrium supplies the glycolytic products to the mitochondrial matrix for OXPHOS. LDH in the mitochondrial matrix is not compatible with the cytoplasmic/matrix redox gradient; its presence would drain matrix reducing power and substantially dissipate the proton motive force. OXPHOS requires O2 as the final electron acceptor, but O2 s upply is sufficient in most situations, including exercise and often acute illness. Recent studies suggest that atmospheric normoxia may constitute a cellular hyperoxia in mitochondrial disease. As research proceeds appropriate oxygenation levels should be carefully considered. Abstract figure legend Credit for the discovery of what would become known as mitochondria is given to Rudolf Albrecht von Kölliker in 1857; these structures were subsequently described in greater detail by Richard Altmann. In 1898, Benda used a derivation of the Greek words for 'thread' and 'granule' to name these structures 'mitochondria'. In 1907, Fletcher and Hopkins reported the disappearance of lactate in the presence of O2 in previously stimulated muscles. Approximately two decades later, Meyerhof's work on O2 consumption and lactate (La- ) resynthesis into glycogen during the recovery of isolated skeletal muscles from prior contractions was an early hint at the intersection of glycolysis and aerobic phosphorylation. Warburg related these phenomena to the metabolic physiology of cancer. Research by both Meyerhof and Emden led to discovery of the glycolytic pathway. In the 1930s, the work of Lundsgaard, Krebs, Kalckar, the Coris, Belitzer and Szent-Gyorgi, and subsequently Lipmann, Ochoa, Bensley & Hoerr and Claude in the 1940s led to establishing the bioenergetics of glycolysis and the TCA cycle and compounds of high phosphoryl transfer potential. The 1950s heralded the age of research using isolated, functioning mitochondria to explore bioenergetics, and featured prominently the work of Lehninger, Estabrook & Saktor, and Chance & Williams. In the 1960s, Peter Mitchell first proposed the chemiosmotic theory of oxidative phosphorylation, for which he was awarded the Nobel Prize. During this same decade, work by Borst clarified the malate-aspartate shuttle, wherein the exchange of anionic aspartate for undissociated glutamate (one negative charge exported from the matrix per exchange) is driven by the membrane potential (ΔΨ). Work by Skulachev in this decade and beyond further clarified mitochondrial bioenergetics and mitochondrial morphology. Boyer elucidated the nature of the ATP synthase, ultimately winning the Nobel Prize for his work. In the 1980s, David Nicholls further clarified mitochondrial bioenergetics, and the work of George Brooks initiated the era of the Cell-to-Cell Lactate Shuttle. Starting in the 1990s, research emerged suggesting that mitochondria are capable of transporting La- across the inner membrane and oxidizing it without the support of the cytosolic-mitochondrial electron shuttles (i.e. the malate-aspartate and glycerol-3-phosphate shuttles). The ultimate combustion of La- obviously takes place in the mitochondria; there is no question about that simple conclusion. However, our view is that La- is not directly oxidized by LDH in the mitochondrial matrix, but rather La- must first be converted to pyruvate (Pyr- ) in the cytosol or intermembrane space. Rationale for this view includes the high activity of the near-equilibrium enzyme LDH, which exceeds glycolytic capacity, the highly oxidized NAD+ /NADH ratio relative to the mitochondrial matrix, and the thermodynamic necessity for an energy-driven accumulation of shuttle species (e.g. ΔΨ-dependent aspartate-glutamate exchanger). Modeling in silico demonstrates that an active LDH in the matrix would render mitochondria nearly incapable of oxidizing Pyr- , a result which is inconsistent with decades of studies from hundreds of laboratories using both isolated mitochondria and permeabilized cells in which the mitochondrial reticulum remains intact. Healthy mitochondria function well, even at low O2 levels such that dysoxia is rare and low O2 is likely a minor factor in the increasing concentrations of La- typical with exercise or even many acute critical care situations.2 This article is protected by copyright. All rights reserved.
  9. J Appl Physiol (1985). 2020 Apr 30.
    Gorgey AS, Graham ZA, Chen Q, Rivers JF, Adler RA, Lesnefsky EJ, Cardozo CP.
      We investigated the effects of testosterone replacement therapy (TRT) with and without evoked resistance training (RT) on protein expression of key metabolic and hypertrophy regulators, muscle fiber cross sectional area (CSA) and markers of mitochondrial health after spinal cord injury (SCI). Twenty-two men with chronic motor complete SCI were randomly assigned to either TRT+RT (n = 11) or TRT (n = 11) for 16 weeks. TRT+RT men underwent twice weekly progressive RT using electrical stimulation with ankle weights. TRT was administered via testosterone patches (2-6 mg/day). Muscle biopsies were obtained before and after 16 weeks from the right vastus lateralis. Expression of proteins associated with oxidative muscles and mechanical loading (PGC1α and FAK), muscle hypertrophy (total and phosphorylated AKT, total and phosphorylated mTOR), and cellular metabolism (total and phosphorylated AMPK and GLUT4) were evaluated. Immunohistochemistry analysis was performed to measure fiber CSA, and succinate dehydrogenase (SDH) activity as well as mitochondrial citrate synthase (CS) activity and complex III (CIII)activities. TRT+RT demonstrated a robust 27.5% increase in average fiber CSA compared to -9% decreased following TRT only (P=0.01). GLUT4 protein expression was elevated in the TRT+RT group compared to the TRT only (P=0.005). Total Akt (P=0.06) and phosphorylated AktSer389 (P=0.049) were also elevated in the TRT+RT group. Mitochondrial activity of SDH (P =0.03) and CS (P=0.006) increased in TRT+RT group with no changes in TRT only group. Sixteen weeks of TRT with RT resulted in fiber hypertrophy and beneficial changes in markers of skeletal muscle health and function.
    Keywords:  mitochondrial health; muscle hypertrophy; resistance training; spinal cord injury; testosterone
  10. J Cell Biol. 2020 Jul 06. pii: e201909165. [Epub ahead of print]219(7):
    Ho N, Yap WS, Xu J, Wu H, Koh JH, Goh WWB, George B, Chong SC, Taubert S, Thibault G.
      Membrane integrity at the endoplasmic reticulum (ER) is tightly regulated, and its disturbance is implicated in metabolic diseases. Using an engineered sensor that activates the unfolded protein response (UPR) exclusively when normal ER membrane lipid composition is compromised, we identified pathways beyond lipid metabolism that are necessary to maintain ER integrity in yeast and in C. elegans. To systematically validate yeast mutants that disrupt ER membrane homeostasis, we identified a lipid bilayer stress (LBS) sensor in the UPR transducer protein Ire1, located at the interface of the amphipathic and transmembrane helices. Furthermore, transcriptome and chromatin immunoprecipitation analyses pinpoint the UPR as a broad-spectrum compensatory response wherein LBS and proteotoxic stress deploy divergent transcriptional UPR programs. Together, these findings reveal the UPR program as the sum of two independent stress responses, an insight that could be exploited for future therapeutic intervention.
  11. Pharmacol Res. 2020 Apr 24. pii: S1043-6618(20)31154-3. [Epub ahead of print] 104846
    Liang X, Wang S, Wang L, Ceylan AF, Ren J, Zhang Y.
      Doxorubicin (DOX) is one of the most effective antineoplastic drugs. However, its clinical application has been greatly limited due to the development of cardiotoxicity with DOX utilization. A number of theories have been postulated for DOX-induced cardiotoxicity with a pivotal contribution from unchecked (excess) mitophagy and mitochondrial fission. Liensinine (LIEN), a newly identified mitophagy inhibitor, strengthens the antineoplastic efficacy of DOX although its action on hearts remains elusive. This study was designed to examine the effect of LIEN on DOX-induced cardiotoxicity and the underlying mechanisms involved with a focus on mitochondrial dynamics. Our data revealed that LIEN alleviated DOX-induced cardiac dysfunction and apoptosis through inhibition of dynamin-related protein 1 (Drp1)-mediated excess (unchecked) mitochondrial fission. LIEN treatment decreased Drp1 phosphorylation at Ser616 site, inhibited mitochondrial fragmentation, mitophagy (assessed by TOM20 and TIM23), oxidative stress, cytochrome C leakage, cardiomyocyte apoptosis, as well as improved mitochondrial function and cardiomyocyte contractile function in DOX-induced cardiac injury. In DOX-challenged neonatal mouse ventricular myocytes (NMVMs), LIEN-suppressed Drp1 phosphorylation, mitochondrial fragmentation, and apoptosis were blunted by Rab7 overexpression, the effect of which was reversed by the ERK inhibitor U0126. Moreover, activation of ERK or Drp1 abolished the protective effects of LIEN on cardiomyocyte mechanical anomalies. These data shed some lights towards understanding the role of LIEN as a new protective agent against DOX-associated cardiotoxicity without compromising its anti-tumor effects.
    Keywords:  cardioprotection; doxorubicin; liensinine; mitochondrial fission; mitophagy
  12. Physiol Rep. 2020 May;8(9): e14408
    Jannas-Vela S, Klingel SL, Cervone DT, Wickham KA, Heigenhauser GJF, Mutch DM, Holloway GP, Spriet LL.
      Omega-3 polyunsaturated fatty acids (PUFAs) have unique properties purported to influence several aspects of metabolism, including energy expenditure and protein function. Supplementing with n-3 PUFAs may increase whole-body resting metabolic rate (RMR), by enhancing Na+ /K+ ATPase (NKA) activity and reducing the efficiency of sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA) activity by inducing a Ca2+ leak-pump cycle. The purpose of this study was to examine the effects of fish oil (FO) on RMR, substrate oxidation, and skeletal muscle SERCA and NKA pump function in healthy older individuals. Subjects (n = 16 females; n = 8 males; 65 ± 1 years) were randomly assigned into groups supplemented with either olive oil (OO) (5 g/day) or FO (5 g/day) containing 2 g/day eicosapentaenoic acid and 1 g/day docosahexaenoic acid for 12 weeks. Participants visited the laboratory for RMR and substrate oxidation measurements after an overnight fast at weeks 0 and 12. Skeletal muscle biopsies were taken during weeks 0 and 12 for analysis of NKA and SERCA function and protein content. There was a main effect of time with decrease in RMR (5%) and fat oxidation (18%) in both the supplementation groups. The kinetic parameters of SERCA and NKA maximal activity, as well as the expression of SR and NKA proteins, were not affected after OO and FO supplementation. In conclusion, these results suggest that FO supplementation is not effective in altering RMR, substrate oxidation, and skeletal muscle SERCA and NKA protein levels and activities, in healthy older men and women.
    Keywords:  Na+/K+ ATPase; SERCA; omega-3; resting metabolic rate; skeletal muscle
  13. Trends Cell Biol. 2020 Apr 25. pii: S0962-8924(20)30093-3. [Epub ahead of print]
    Eldeeb MA, Bayne AN, Trempe JF, Fon EA.
      Given their polyvalent functions, an inherent challenge that mitochondria face is the exposure to mitochondrial import stresses, culminating in their dysfunction. Recently, mitochondrial import of several mitochondrial substrates was shown to be regulated via a 'tug of war' between USP30 and MARCH5, two ubiquitin-related enzymes located at the TOM complex.
    Keywords:  MARCH5; TOM complex; USP30; mitochondrial quality control; proteasome; protein degradation; protein quality control; ubiquitin
  14. Neuromuscul Disord. 2020 Feb 28. pii: S0960-8966(20)30055-9. [Epub ahead of print]
    Roussel MP, Hébert LJ, Duchesne E.
      Myotonic dystrophy type 1 (DM1) is a multisystemic disease characterized by progressive muscle weakness. The aim of this project is to evaluate the effects of a 12-week lower limb strength training program in 11 men with DM1. Maximal isometric muscle strength, 30-second sit-to-stand, comfortable and maximal 10-m walk test (10 mwt) were evaluated at baseline, 6 and 12 weeks, and at 6 and 9 months. The one-repetition maximum strength evaluation method of the training exercises was completed at baseline, 6 and 12 weeks. Muscle biopsies were taken in the vastus lateralis at baseline and 12 weeks to evaluate muscle fiber typing and size (including atrophy/hypertrophy factors). Performance in strength and functional tests all significantly improved by week 12. Maximal isometric muscle strength of the knee extensors decreased by month 9, while improved walking speed and 30 second sit-to-stand performance were maintained. On average, there were no significant changes in fiber typing or size after training. Further analysis showed that individual abnormal hypertrophy factor at baseline could explain the different changes in muscle size among participants. Strength training induces maximal isometric muscle strength and lasting functional gains in DM1. Abnormal hypertrophy factor could be a key component to identify high and low responders to hypertrophy in DM1.
    Keywords:  1- myotonic dystrophy; 2- strength training; 3- muscle strength; 4- functional capacity; 5- muscle fiber size
  15. Cell Struct Funct. 2020 Apr 29.
    Back SH.
      It is often assumed that α-subunit phosphorylation of the eukaryotic translation initiation factor 2 (eIF2) complex is just a mechanism to control protein synthesis. However, eIF2α phosphorylation induced by multiple kinases can recognize various intracellular and extracellular stress conditions, and it is involved in various other cellular processes beyond protein synthesis. This review introduces the roles of eIF2α phosphorylation in translational regulation, the generation of reactive oxygen species, changes in mitochondria structure and shape, and mitochondrial retrograde signaling pathways in response to diverse stress conditions. Key words: eIF2α phosphorylation, Translation, Unfolded Protein Response, Reactive Oxygen Species, Mitochondria.
    Keywords:  Mitochondria; Reactive Oxygen Species; Translation; Unfolded Protein Response; eIF2α phosphorylation
  16. J Mol Cell Cardiol. 2020 Apr 27. pii: S0022-2828(20)30119-X. [Epub ahead of print]
    Garbincius JF, Luongo TS, Elrod JW.
      Since the initial identification of the mitochondrial calcium uniporter (MCU) in 2011, several studies employing genetic models have attempted to decipher the role of mitochondrial calcium uptake in cardiac physiology. Confounding results in various mutant mouse models have led to an ongoing debate regarding the function of MCU in the heart. In this review, we evaluate and discuss the totality of evidence for mitochondrial calcium uptake in the cardiac stress response. We highlight recent reports that implicate MCU in the control of homeostatic cardiac metabolism and function. This review concludes with a discussion of current gaps in knowledge and remaining experiments to define how MCU contributes to contractile function, cell death, metabolic regulation, and heart failure progression.
    Keywords:  Calcium; Cardiac function; Energetics; Ischemia reperfusion; MCU; MICU1; Mitochondria; NCLX; Permeability transition