J Physiol Volume 586, Number 11, 2675-2681, June 1, 2008 DOI: 10.1113/jphysiol.2008.154369
Nuclear domains during muscle atrophy: nuclei lost or paradigm lost?
Kristian Gundersen1 and
Jo C. Bruusgaard1
1 Department of Molecular Biosciences, University of Oslo, PO Box 1041 Blindern, N-0316 Oslo, Norway
According to the current paradigm, muscle nuclei serve a certain cytoplasmic domain. To preserve the domain size, it is believed that nuclei are injected from satellite cells fusing to fibres undergoing hypertrophy, and lost by apoptosis during atrophy. Based on single fibre observations in and ex vivo we suggest that nuclear domains are not as constant as is often indicated. Moreover, recent time lapse in vivo imaging of single fibres suggests that at least for the first few weeks, atrophy is not accompanied by any loss of nuclei. Apoptosis is abundant in muscle tissue during atrophy conditions, but in our opinion it has not been unequivocally demonstrated that such nuclei are myonuclei. As we see it, the preponderance of current evidence suggests that disuse atrophy is not accompanied by loss of nuclei, at least not for the first 2 months. Moreover, it has not been proven that myonuclear apoptosis does occur in permanent fibres undergoing atrophy; it seems more likely that it is confined to stromal cells and satellite cells. If muscle atrophy is not related to loss of nuclei, design of intervention therapies should focus on protein metabolism rather than regeneration from stem cells.
(Received 20 March 2008;
accepted after revision 15 April 2008;
first published online 25 April 2008)
Corresponding author K. Gundersen: Department of Molecular Biosciences, University of Oslo, PO Box 1041 Blindern, N-0316 Oslo, Norway. Email: kgunder{at}imbv.uio.no
Copyright © 2008 The Physiological Society.
