title: Exploring the Role of PGC-1α in Defining Nuclear Organisation in Skeletal Muscle Fibres.
abstract: Muscle fibres are multinucleated cells, with each nucleus controlling the protein synthesis in a finite volume of cytoplasm termed the myonuclear domain (MND). What determines MND size remains unclear. In the present study, we aimed to test the hypothesis that the level of expression of the transcriptional coactivator PGC-1α and subsequent activation of the mitochondrial biogenesis are major contributors. Hence, we used two transgenic mouse models with varying expression of PGC-1α in skeletal muscles. We isolated myofibres from the fast twitch extensor digitorum longus (EDL) and slow twitch diaphragm muscles. We then membrane-permeabilised them and analysed the 3D spatial arrangements of myonuclei. In EDL muscles, when PGC-1α is over-expressed, MND volume decreases; whereas, when PGC-1α is lacking, no change occurs. In the diaphragm, no clear difference was noted. This indicates that PGC-1α and the related mitochondrial biogenesis programme are determinants of MND size. PGC-1α may facilitate the addition of new myonuclei in order to reach MND volumes that can support an increased mitochondrial density. J. Cell. Physiol. 232: 1270-1274, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Centre of Human and Aerospace Physiological Sciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Ross
authors.affiliation: Centre of Human and Aerospace Physiological Sciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Pearson
authors.affiliation: Centre of Human and Aerospace Physiological Sciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.
authors.forename: Yotam
authors.initials: Y
authors.lastname: Levy
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Bettina
authors.initials: B
authors.lastname: Cardel
authors.affiliation: Biozentrum, University of Basel, Basel, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Handschin
authors.affiliation: Centre of Human and Aerospace Physiological Sciences, Faculty of Life Sciences & Medicine, King's College London, London, UK.
authors.forename: Julien
authors.initials: J
authors.lastname: Ochala
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D053144:Cell Nucleus Shape; D003964:Diaphragm / Q000378:metabolism; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism*
chemical_list: D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse