| First Author | Pauly M | Year | 2017 |
| Journal | Biochim Biophys Acta | Volume | 1863 |
| Issue | 9 | Pages | 2229-2239 |
| PubMed ID | 28625916 | Mgi Jnum | J:256866 |
| Mgi Id | MGI:6104665 | Doi | 10.1016/j.bbadis.2017.06.009 |
| Citation | Pauly M, et al. (2017) ER stress disturbs SR/ER-mitochondria Ca(2+) transfer: Implications in Duchenne muscular dystrophy. Biochim Biophys Acta 1863(9):2229-2239 |
| abstractText | Besides its role in calcium (Ca(2+)) homeostasis, the sarco-endoplamic reticulum (SR/ER) controls protein folding and is tethered to mitochondria. Under pathophysiological conditions the unfolded protein response (UPR) is associated with disturbance in SR/ER-mitochondria crosstalk. Here, we investigated whether ER stress altered SR/ER-mitochondria links, Ca(2+) handling and muscle damage in WT (Wild Type) and mdx mice, the murine model of Duchenne Muscular Dystrophy (DMD). In WT mice, the SR/ER-mitochondria links were decreased in isolated FDB muscle fibers after injection of ER stress activator tunicamycin (TM). Ca(2+) imaging revealed an increase of cytosolic Ca(2+) transient and a decrease of mitochondrial Ca(2+) uptake. The force generating capacity of muscle dropped after TM. This impaired contractile function was accompanied by an increase in autophagy markers and calpain-1 activation. Conversely, ER stress inhibitors restored SR/ER-mitochondria links, mitochondrial Ca(2+) uptake and improved diaphragm contractility in mdx mice. Our findings demonstrated that ER stress-altered SR/ER-mitochondria links, disturbed Ca(2+) handling and muscle function in WT and mdx mice. Thus, ER stress may open up a prospect of new therapeutic targets in DMD. |
