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.
Original language | English (US) |
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Pages (from-to) | 481-500 |
Number of pages | 20 |
Journal | FEBS Journal |
Volume | 285 |
Issue number | 3 |
DOIs | |
State | Published - Feb 2018 |
Bibliographical note
Publisher Copyright:© 2017 Federation of European Biochemical Societies
Keywords
- isoforms
- mitochondrial dynamics
- β-actin
- γ-actin