bims-misrem Biomed News
on Mitochondria and sarcoplasmic reticulum in muscle mass
Issue of 2020‒09‒27
nine papers selected by
Rafael Antonio Casuso Pérez
University of Granada

  1. Cell Calcium. 2020 Sep 11. pii: S0143-4160(20)30130-5. [Epub ahead of print]92 102288
      Calcium (Ca2+) is known to stimulate mitochondrial bioenergetics through the modulation of TCA cycle dehydrogenases and electron transport chain (ETC) complexes. This is hypothesized to be an essential pathway of energetic control to meet cellular ATP demand. While regulatory mechanisms of mitochondrial calcium uptake have been reported, it remains unknown if metabolite flux itself feedsback to regulate mitochondrial calcium (mCa2+) uptake. This hypothesis was recently tested by Nemani et al. (Sci. Signal. 2020) where the authors report that TCA cycle substrate flux regulates the mitochondrial calcium uniporter channel gatekeeper, mitochondrial calcium uptake 1 (MICU1), gene transcription in an early growth response protein 1 (EGR1) dependent fashion. They posit this is a regulatory feedback mechanism to control ionic homeostasis and mitochondrial bioenergetics with changing fuel availability. Here, we provide a historical overview of mitochondrial calcium exchange and comprehensive appraisal of these results in the context of recent literature and discuss possible regulatory pathways of mCa2+ uptake and mitochondrial bioenergetics.
    Keywords:  Calcium; Energetics; MCU; MICU1; MPC; Mitochondria; OXPHOS; TCA cycle; TCA substrates
  2. J Physiol. 2020 Sep 22.
      KEY POINTS: The risk of cardiovascular disease and associated skeletal muscle microvascular rarefaction is enhanced in women after menopause, yet knowledge about the angiogenic potential in ageing women is generally sparse. Aged healthy and sedentary women were found to present a markedly impaired capacity for proliferation of skeletal muscle derived microvascular endothelial cells compared to young women. Vascular endothelial growth factor (VEGF) levels in skeletal muscle myocytes and release of VEGF from myocytes tended to be lower in aged compared to young women. The aged women did not show a detectable increase in skeletal muscle capillarization with 8 weeks of intense aerobic cycle training. Combined, the findings indicate that aged women have a reduced potential for capillary growth in skeletal muscle which, with ageing, may lead to age-induced microvascular rarefaction.ABSTRACT: Skeletal muscle angiogenic potential was examined in cell cultures derived from aged and young women, and the effect of 8 weeks of intense cycle training on muscle capillary growth was determined in the group of aged women. Basal muscle samples were obtained from healthy sedentary aged (n = 12; 64 ± 4.2 years) and young women (n = 5; 24 ± 3.2 years) for endothelial cell and skeletal muscle myocyte isolation and experiments. In addition, the aged women completed an 8-week training intervention. Peak oxygen uptake and muscle samples for histology and protein determination were obtained before and after the training period. Before training, muscle microdialysate was collected from the aged women at rest and during exercise. In Part 1 of the experiments, growth-supplement stimulated proliferation of endothelial cells was ∼75% lower in cells from aged compared to young women (P < 0.001). There was a tendency for a lower vascular endothelial growth factor (VEGF) concentration in muscle conditioned media (P = 0.0696) and for a lower VEGF content in the myocytes (P = 0.0705) from aged compared to young women. Endothelial proliferation was found to be highly dependent on mitochondrial function. Acute exercise resulted in a modest (1.3-fold; P = 0.0073) increase in muscle interstitial VEGF protein in the aged women. In Part 2, 8 weeks of intense training did not change muscle capillarization (P ≥ 0.1502) in the aged women, but led to an increased amount of muscle VEGF (P = 0.0339). In conclusion, aged women have impaired angiogenic potential, which is associated with a compromised response both at the skeletal muscle myocyte and microvascular endothelial cell level.
    Keywords:  aged women; capillary growth; microvascular endothelial cells; proliferation; skeletal muscle; vascular endothelial growth factor
  3. Curr Opin Cell Biol. 2020 Sep 19. pii: S0955-0674(20)30111-3. [Epub ahead of print]68 28-36
      Mitochondria form networks that continually remodel and adapt to carry out their cellular function. The mitochondrial network is remodeled through changes in mitochondrial morphology, number, and distribution within the cell. Mitochondrial dynamics depend directly on fission, fusion, shape transition, and transport or tethering along the cytoskeleton. Over the past several years, many of the mechanisms underlying these processes have been uncovered. It has become clear that each process is precisely and contextually regulated within the cell. Here, we discuss the mechanisms regulating each aspect of mitochondrial dynamics, which together shape the network as a whole.
    Keywords:  Cytoskeleton; Fission; Fusion; Mitochondria; Morphology; Transport
  4. FASEB J. 2020 Sep 23.
      Thyroid hormones are important for homeostatic control of energy metabolism and body temperature. Although skeletal muscle is considered a key site for thyroid action, the contribution of thyroid hormone receptor signaling in muscle to whole-body energy metabolism and body temperature has not been resolved. Here, we show that T3-induced increase in energy expenditure requires thyroid hormone receptor alpha 1 (TRα1 ) in skeletal muscle, but that T3-mediated elevation in body temperature is achieved in the absence of muscle-TRα1 . In slow-twitch soleus muscle, loss-of-function of TRα1 (TRαHSACre ) alters the fiber-type composition toward a more oxidative phenotype. The change in fiber-type composition, however, does not influence the running capacity or motivation to run. RNA-sequencing of soleus muscle from WT mice and TRαHSACre mice revealed differentiated transcriptional regulation of genes associated with muscle thermogenesis, such as sarcolipin and UCP3, providing molecular clues pertaining to the mechanistic underpinnings of TRα1 -linked control of whole-body metabolic rate. Together, this work establishes a fundamental role for skeletal muscle in T3-stimulated increase in whole-body energy expenditure.
    Keywords:  energy expenditure; energy metabolism; skeletal muscle; thyroid hormone
  5. Nat Rev Endocrinol. 2020 Sep 22.
      Both the consumption of a diet rich in fatty acids and exercise training result in similar adaptations in several skeletal muscle proteins. These adaptations are involved in fatty acid uptake and activation within the myocyte, the mitochondrial import of fatty acids and further metabolism of fatty acids by β-oxidation. Fatty acid availability is repeatedly increased postprandially during the day, particularly during high dietary fat intake and also increases during, and after, aerobic exercise. As such, fatty acids are possible signalling candidates that regulate transcription of target genes encoding proteins involved in muscle lipid metabolism. The mechanism of signalling might be direct or indirect targeting of peroxisome proliferator-activated receptors by fatty acid ligands, by fatty acid-induced NAD+-stimulated activation of sirtuin 1 and/or fatty acid-mediated activation of AMP-activated protein kinase. Lactate might also have a role in lipid metabolic adaptations. Obesity is characterized by impairments in fatty acid oxidation capacity, and individuals with obesity show some rigidity in increasing fatty acid oxidation in response to high fat intake. However, individuals with obesity retain improvements in fatty acid oxidation capacity in response to exercise training, thereby highlighting exercise training as a potential method to improve lipid metabolic flexibility in obesity.
  6. FEBS J. 2020 Sep 22.
      Mitochondrial protein homeostasis is crucial for cellular health and perturbations have been linked to a plethora of human diseases. Proteostasis is maintained mainly by a network of mitochondrial chaperones and proteases, that assist in protein folding and degrade non-functional or superfluous proteins. Upon proteomic imbalances or defects in mitochondrial functions protective cellular responses are activated to restore and maintain organellar integrity. This viewpoint describes our current knowledge and understanding of these protective pathways and addresses open questions and perspectives in the field of mitochondrial stress responses.
    Keywords:  Mitochondrial proteostasis; integrated stress response; mitochondrial dysfunction; mitochondrial protein biogenesis
  7. J Appl Physiol (1985). 2020 Sep 24.
      The purpose of this investigation was to evaluate the effects of aging and lifelong exercise on skeletal muscle components of the innate immune system. Additionally, the effects of an acute resistance exercise (RE) challenge were explored. Three groups of men were studied: young exercisers (YE, n=10, 25±1y, VO2max:53±3mL/kg/min, quadriceps size:78±3cm2), lifelong aerobic exercisers with a 53±1y training history (LLE, n=21, 74±1y, VO2max:34±1 mL/kg/min, quadriceps size:67±2cm2), and old healthy non-exercisers (OH, n=10, 75±1y, VO2max:22±1mL/kg/min, quadriceps size:56±3cm2). Vastus lateralis muscle biopsies were obtained in the basal state and 4h after RE (3x10reps, 70%1RM) to assess Toll-like receptors (TLR)1-10, TLR adaptors (Myd88 and TRIF), and NFκB pathway components (IκΒα and IKKβ) mRNA expression. Basal TLR3, TLR6, and TLR7 tended to be higher (P≤0.10) with aging (LLE and OH combined). In general, RE increased expression of TLR1 and TLR8 (P≤0.10) and TLR3 and TLR4 (P<0.05), although TLR3 did not respond in OH. Both TLR adaptors also responded to the exercise bout; these were primarily (Myd88, main effect P≤0.10) or exclusively (TRIF, P<0.05) driven by the OH group. In summary, aging appears to increase basal expression of some innate immune components in human skeletal muscle, and lifelong aerobic exercise does not affect this age-related increase. An exercise challenge stimulates the expression of several TLRs, while the TLR adaptor response appears to be dysregulated with aging and maintained with lifelong exercise. Partially preserved muscle mass, coupled with a notable immunity profile, suggests lifelong exercisers are likely better prepared for a stress that challenges the immune system.
    Keywords:  Aging; Innate Immunity; Lifelong Exercise; Skeletal Muscle; TLR
  8. J Transl Med. 2020 Sep 25. 18(1): 367
      The existence of active crosstalk between cells in a paracrine and juxtacrine manner dictates specific activity under physiological and pathological conditions. Upon juxtacrine interaction between the cells, various types of signaling molecules and organelles are regularly transmitted in response to changes in the microenvironment. To date, it has been well-established that numerous parallel cellular mechanisms participate in the mitochondrial transfer to modulate metabolic needs in the target cells. Since the conception of stem cells activity in the restoration of tissues' function, it has been elucidated that these cells possess a unique capacity to deliver the mitochondrial package to the juxtaposed cells. The existence of mitochondrial donation potentiates the capacity of modulation in the distinct cells to achieve better therapeutic effects. This review article aims to scrutinize the current knowledge regarding the stem cell's mitochondrial transfer capacity and their regenerative potential.
    Keywords:  Cellular mechanisms; Mitochondrial transfer; Regenerative potential; Stem cells
  9. Trends Cell Biol. 2020 Sep 22. pii: S0962-8924(20)30169-0. [Epub ahead of print]
      Mitochondria are dynamic organelles that have essential metabolic and regulatory functions. Earlier studies using electron microscopy (EM) revealed an immense diversity in the architecture of cristae - infoldings of the mitochondrial inner membrane (IM) - in different cells, tissues, bioenergetic and metabolic conditions, and during apoptosis. However, cristae were considered to be largely static entities. Recently, advanced super-resolution techniques have revealed that cristae are independent bioenergetic units that are highly dynamic and remodel on a timescale of seconds. These advances, coupled with mechanistic and structural studies on key molecular players, such as the MICOS (mitochondrial contact site and cristae organizing system) complex and the dynamin-like GTPase OPA1, have changed our view on mitochondria in a fundamental way. We summarize these recent findings and discuss their functional implications.
    Keywords:  MICOS; OPA1; cristae dynamics; remodeling