| First Author | O'Rourke AR | Year | 2018 |
| Journal | FEBS J | Volume | 285 |
| Issue | 3 | Pages | 481-500 |
| PubMed ID | 29265728 | Mgi Jnum | J:318614 |
| Mgi Id | MGI:6851067 | Doi | 10.1111/febs.14367 |
| Citation | O'Rourke AR, et al. (2018) Impaired muscle relaxation and mitochondrial fission associated with genetic ablation of cytoplasmic actin isoforms. FEBS J 285(3):481-500 |
| abstractText | While alpha-actin isoforms predominate in adult striated muscle, skeletal muscle-specific knockouts (KOs) of nonmuscle cytoplasmic betacyto - or gammacyto -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 betacyto - and gammacyto -actin KO mice. We found betacyto - and gammacyto -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 betacyto - and/or gammacyto -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 betacyto - and gammacyto -actin KO mice. Instead, we found that the maximal rate of relaxation after isometric contraction was significantly slowed in muscles of 12-month-old betacyto - and gammacyto -actin muscle-specific KO mice. Our data suggest that impaired Ca(2+) re-uptake may presage development of the observed SR morphological changes in aged mice while providing a potential pathological mechanism for the observed myopathy. |
