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Exploring the Role of PGC-1α in Defining Nuclear Organisation in Skeletal Muscle Fibres

Research output: Contribution to journalArticle

Jacob Alexander Ross, Adam Pearson, Yotam Levy, Bettina Cardel, Christoph Handschin, Julien Ochala

Original languageEnglish
JournalJournal of Cellular Physiology
Early online date7 Nov 2016
DOIs
Accepted/In press3 Nov 2016
E-pub ahead of print7 Nov 2016
Published29 Dec 2016

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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.

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