[
J Cell Biol,
2006]
Fibulin is a broadly conserved component of the extracellular matrix (ECM). Previous studies have shown that Caenorhabditis elegans FIBULIN-1 (FBL-1) controls the width of the gonad (Hesselson, D., C. Newman, K.W. Kim, and J. Kimble. 2004. Curr. Biol. 14:2005-2010; Kubota, Y., R. Kuroki, and K. Nishiwaki. 2004. Curr. Biol. 14:2011-2018; Muriel, J.M., C. Dong, H. Hutter, and B.E. Vogel. 2005. Development. 132: 4223-4234). In this study, we report that FBL-1 also controls developmental growth and that one isoform of fibulin-1, called FBL-1C, controls both functions by distinct mechanisms. A large FBL-1C fragment, including both epidermal growth factor (EGF) and fibulin-type C domains, is responsible for constraining gonadal width, but a much smaller fragment containing only two complete EGF repeats (EGF1-2C+) is critical for developmental growth. We suggest that the larger fragment serves a scaffolding function to stabilize the basement membrane and that the smaller fragment provides a regulatory function at the cell surface or within the ECM to control growth.
[
FASEB J,
2019]
Mitochondrial dysfunction impairs muscle health and causes subsequent muscle wasting. This study explores the role of mitochondrial dysfunction as an intramuscular signal for the extracellular matrix (ECM)-based proteolysis and, consequentially, muscle cell dystrophy. We found that inhibition of the mitochondrial electron transport chain causes paralysis as well as muscle structural damage in the nematode <i>Caenorhabditis elegans</i>. This was associated with a significant decline in collagen content. Both paralysis and muscle damage could be rescued with collagen IV overexpression, matrix metalloproteinase (MMP), and Furin inhibitors in Antimycin A-treated animal as well as in the <i>C. elegans</i> Duchenne muscular dystrophy model. Additionally, muscle cytosolic calcium increased in the Antimycin A-treated worms, and its down-regulation rescued the muscle damage, suggesting that calcium overload acts as one of the early triggers and activates Furin and MMPs for collagen degradation. In conclusion, we have established ECM degradation as an important pathway of muscle damage.-Sudevan, S., Takiura, M., Kubota, Y., Higashitani, N., Cooke, M., Ellwood, R. A., Etheridge, T., Szewczyk, N. J., Higashitani, A. Mitochondrial dysfunction causes Ca<sup>2+</sup> overload and ECM degradation-mediated muscle damage in <i>C. elegans</i>.