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FEBS J. 2018 Feb;285(3):481-500. doi: 10.1111/febs.14367. Epub 2018 Jan 8.

Impaired muscle relaxation and mitochondrial fission associated with genetic ablation of cytoplasmic actin isoforms.

Author information

1
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN, USA.
2
Department of Rehabilitation Medicine, University of Minnesota, Minneapolis, MN, USA.
3
Department of Physiology, East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC, USA.
4
Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN, USA.
5
Department of Biology, Indiana University-Purdue University Indianapolis, IN, USA.

Abstract

While α-actin isoforms predominate in adult striated muscle, skeletal muscle-specific knockouts (KOs) of nonmuscle cytoplasmic βcyto - or γcyto -actin each cause a mild, but progressive myopathy effected by an unknown mechanism. Using transmission electron microscopy, we identified morphological abnormalities in both the mitochondria and the sarcoplasmic reticulum (SR) in aged muscle-specific βcyto - and γcyto -actin KO mice. We found βcyto - and γcyto -actin proteins to be enriched in isolated mitochondrial-associated membrane preparations, which represent the interface between mitochondria and sarco-endoplasmic reticulum important in signaling and mitochondrial dynamics. We also measured significantly elongated and interconnected mitochondrial morphologies associated with a significant decrease in mitochondrial fission events in primary mouse embryonic fibroblasts lacking βcyto - and/or γcyto -actin. Interestingly, mitochondrial respiration in muscle was not measurably affected as oxygen consumption was similar in skeletal muscle fibers from 12 month-old muscle-specific βcyto - and γcyto -actin KO mice. Instead, we found that the maximal rate of relaxation after isometric contraction was significantly slowed in muscles of 12-month-old βcyto - and γcyto -actin muscle-specific KO mice. Our data suggest that impaired Ca2+ re-uptake may presage development of the observed SR morphological changes in aged mice while providing a potential pathological mechanism for the observed myopathy.

KEYWORDS:

isoforms; mitochondrial dynamics; β-actin; γ-actin

PMID:
29265728
PMCID:
PMC5799018
DOI:
10.1111/febs.14367
[Indexed for MEDLINE]
Free PMC Article

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