bims-misrem Biomed News
on Mitochondria and sarcoplasmic reticulum in muscle mass
Issue of 2020‒10‒25
seven papers selected by
Rafael Antonio Casuso Pérez
University of Granada

  1. Cell Mol Life Sci. 2020 Oct 19.
    Romanello V, Sandri M.
      The dynamic coordination of processes controlling the quality of the mitochondrial network is crucial to maintain the function of mitochondria in skeletal muscle. Changes of mitochondrial proteolytic system, dynamics (fusion/fission), and mitophagy induce pathways that affect muscle mass and performance. When muscle mass is lost, the risk of disease onset and premature death is dramatically increased. For instance, poor quality of muscles correlates with the onset progression of several age-related disorders such as diabetes, obesity, cancer, and aging sarcopenia. To date, there are no drug therapies to reverse muscle loss, and exercise remains the best approach to improve mitochondrial health and to slow atrophy in several diseases. This review will describe the principal mechanisms that control mitochondrial quality and the pathways that link mitochondrial dysfunction to muscle mass regulation.
    Keywords:  Atrophy; Autophagy; FGF21; Fission; Fusion; Mitochondria; Mitochondrial proteostasis; Mitophagy; Myokines; Skeletal muscle
  2. J Cell Biol. 2020 Dec 07. pii: e202002144. [Epub ahead of print]219(12):
    English AM, Schuler MH, Xiao T, Kornmann B, Shaw JM, Hughes AL.
      Mitochondria are dynamic organelles with essential roles in signaling and metabolism. We recently identified a cellular structure called the mitochondrial-derived compartment (MDC) that is generated from mitochondria in response to amino acid overabundance stress. How cells form MDCs is unclear. Here, we show that MDCs are dynamic structures that form and stably persist at sites of contact between the ER and mitochondria. MDC biogenesis requires the ER-mitochondria encounter structure (ERMES) and the conserved GTPase Gem1, factors previously implicated in lipid exchange and membrane tethering at ER-mitochondria contacts. Interestingly, common genetic suppressors of abnormalities displayed by ERMES mutants exhibit distinct abilities to rescue MDC formation in ERMES-depleted strains and are incapable of rescuing MDC formation in cells lacking Gem1. Thus, the function of ERMES and Gem1 in MDC biogenesis may extend beyond their conventional role in maintaining mitochondrial phospholipid homeostasis. Overall, this study identifies an important function for ER-mitochondria contacts in the biogenesis of MDCs.
  3. Ageing Res Rev. 2020 Oct 15. pii: S1568-1637(20)30328-7. [Epub ahead of print]64 101193
    Gil-Hernández A, Silva-Palacios A.
      Although the elixir of youth remains in the darkness, medical and scientific advances have succeeded in increasing human longevity; however, the predisposition to disease and its high economic cost are raising. Different strategies (e.g., antioxidants) and signaling pathways (e.g., Nrf2) have been identified to help regulate disease progression, nevertheless, there are still missing links that we need to understand. Contact sites called mitochondria-associated membranes (MAM) allow bi-directional communication between organelles as part of the essential functions in the cell to maintain its homeostasis. Different groups have deeply studied the role of MAM in aging; however, it's necessary to analyze their involvement in the progression of age-related diseases. In this review, we highlight the role of contact sites in these conditions, as well as the morphological and functional changes of mitochondria and ER in aging. We emphasize the intimate relationship between both organelles as a reflection of the biological processes that take place in the cell to try to regulate the deterioration characteristic of the aging process; proposing MAM as a potential target to help limit the disease progression with age.
    Keywords:  Aging; MAM; contact site; longevity; membrane; mitochondria; sarco/endoplasmic reticulum
  4. Nat Rev Mol Cell Biol. 2020 Oct 22.
    Song J, Herrmann JM, Becker T.
      Mitochondria contain about 1,000-1,500 proteins that fulfil multiple functions. Mitochondrial proteins originate from two genomes: mitochondrial and nuclear. Hence, proper mitochondrial function requires synchronization of gene expression in the nucleus and in mitochondria and necessitates efficient import of mitochondrial proteins into the organelle from the cytosol. Furthermore, the mitochondrial proteome displays high plasticity to allow the adaptation of mitochondrial function to cellular requirements. Maintenance of this complex and adaptable mitochondrial proteome is challenging, but is of crucial importance to cell function. Defects in mitochondrial proteostasis lead to proteotoxic insults and eventually cell death. Different quality control systems monitor the mitochondrial proteome. The cytosolic ubiquitin-proteasome system controls protein transport across the mitochondrial outer membrane and removes damaged or mislocalized proteins. Concomitantly, a number of mitochondrial chaperones and proteases govern protein folding and degrade damaged proteins inside mitochondria. The quality control factors also regulate processing and turnover of native proteins to control protein import, mitochondrial metabolism, signalling cascades, mitochondrial dynamics and lipid biogenesis, further ensuring proper function of mitochondria. Thus, mitochondrial protein quality control mechanisms are of pivotal importance to integrate mitochondria into the cellular environment.
  5. Trends Cell Biol. 2020 Oct 19. pii: S0962-8924(20)30188-4. [Epub ahead of print]
    Gao S, Hu J.
      Mitochondria are highly dynamic organelles that constantly undergo fission and fusion. Disruption of mitochondrial dynamics undermines their function and causes several human diseases. The fusion of the outer (OMM) and inner mitochondrial membranes (IMM) is mediated by two classes of dynamin-like protein (DLP): mitofusin (MFN)/fuzzy onions 1 (Fzo1) and optic atrophy 1/mitochondria genome maintenance 1 (OPA1/Mgm1). Given the lack of structural information on these fusogens, the molecular mechanisms underlying mitochondrial fusion remain unclear, even after 20 years. Here, we review recent advances in structural studies of the mitochondrial fusion machinery, discuss their implication for DLPs, and summarize the pathogenic mechanisms of disease-causing mutations in mitochondrial fusion DLPs.
    Keywords:  Dynamin superfamily; Mitofusin/Fzo1; OPA1/Mgm1; cristae formation; mitochondrial fusion; structure
  6. Sci Adv. 2020 Oct;pii: eabe5310. [Epub ahead of print]6(43):
    Kory N, Uit de Bos J, van der Rijt S, Jankovic N, Güra M, Arp N, Pena IA, Prakash G, Chan SH, Kunchok T, Lewis CA, Sabatini DM.
      The nicotinamide adenine dinucleotide (NAD+/NADH) pair is a cofactor in redox reactions and is particularly critical in mitochondria as it connects substrate oxidation by the tricarboxylic acid (TCA) cycle to adenosine triphosphate generation by the electron transport chain (ETC) and oxidative phosphorylation. While a mitochondrial NAD+ transporter has been identified in yeast, how NAD enters mitochondria in metazoans is unknown. Here, we mine gene essentiality data from human cell lines to identify MCART1 (SLC25A51) as coessential with ETC components. MCART1-null cells have large decreases in TCA cycle flux, mitochondrial respiration, ETC complex I activity, and mitochondrial levels of NAD+ and NADH. Isolated mitochondria from cells lacking or overexpressing MCART1 have greatly decreased or increased NAD uptake in vitro, respectively. Moreover, MCART1 and NDT1, a yeast mitochondrial NAD+ transporter, can functionally complement for each other. Thus, we propose that MCART1 is the long sought mitochondrial transporter for NAD in human cells.
  7. Biochim Biophys Acta Mol Basis Dis. 2020 Oct 19. pii: S0925-4439(20)30340-9. [Epub ahead of print] 165992
    Alves-Figueiredo H, Silva-Platas C, Lozano O, Vázquez-Garza E, Guerrero-Beltrán CE, Zarain-Herzberg A, García-Rivas G.
      The mitochondrial permeability transition pore (mPTP) opening is involved in the pathophysiology of multiple cardiac diseases, such as ischemia/reperfusion injury and heart failure. A growing number of evidence provided by proteomic screening techniques has demonstrated the role of post-translational modifications (PTMs) in several key components of the pore in response to changes in the extra/intracellular environment and bioenergetic demand. This could lead to a fine, complex regulatory mechanism that, under pathological conditions, can shift the state of mitochondrial functions and, thus, the cell's fate. Understanding the complex relationship between these PTMs is still under investigation and can provide new, promising therapeutic targets and treatment approaches. This review, using a systematic review of the literature, presents the current knowledge on PTMs of the mPTP and their role in health and cardiac disease.
    Keywords:  Mitochondrial permeability transition pore; cardiac disease; cardiac physiology; cardiac physiopathology; diabetic cardiomyopathy; heart failure; ischemia/reperfusion injury; obesity cardiomyopathy; post-translational modifications; systematic review