Calcium and Redox Liaison: A Key Role of Selenoprotein N in Skeletal Muscle
Open Access
- 6 May 2021
- Vol. 10 (5), 1116
- https://doi.org/10.3390/cells10051116
Abstract
Selenoprotein N (SEPN1) is a type II glycoprotein of the endoplasmic reticulum (ER) that senses calcium levels to tune the activity of the sarcoplasmic reticulum calcium pump (SERCA pump) through a redox-mediated mechanism, modulating ER calcium homeostasis. In SEPN1-depleted muscles, altered ER calcium homeostasis triggers ER stress, which induces CHOP-mediated malfunction, altering excitation–contraction coupling. SEPN1 is localized in a region of the ER where the latter is in close contact with mitochondria, i.e., the mitochondria-associated membranes (MAM), which are important for calcium mobilization from the ER to mitochondria. Accordingly, SEPN1-depleted models have impairment of both ER and mitochondria calcium regulation and ATP production. SEPN1-related myopathy (SEPN1-RM) is an inherited congenital muscle disease due to SEPN1 loss of function, whose main histopathological features are minicores, i.e., areas of mitochondria depletion and sarcomere disorganization in muscle fibers. SEPN1-RM presents with weakness involving predominantly axial and diaphragmatic muscles. Since there is currently no disease-modifying drug to treat this myopathy, analysis of SEPN1 function in parallel with that of the muscle phenotype in SEPN1 loss of function models should help in understanding the pathogenic basis of the disease and possibly point to novel drugs for therapy. The present essay recapitulates the novel biological findings on SEPN1 and how these reconcile with the muscle and bioenergetics phenotype of SEPN1-related myopathy.This publication has 56 references indexed in Scilit:
- Endoplasmic reticulum–mitochondria contacts: function of the junctionNature Reviews Molecular Cell Biology, 2012
- Oxidative stress and successful antioxidant treatment in models of RYR1-related myopathyBrain, 2012
- The Unfolded Protein Response: From Stress Pathway to Homeostatic RegulationScience, 2011
- The Unfolded Protein Response Mediates Adaptation to Exercise in Skeletal Muscle through a PGC-1α/ATF6α ComplexCell Metabolism, 2011
- Selenoproteins and Protection against Oxidative Stress: Selenoprotein N as a Novel Player at the Crossroads of Redox Signaling and Calcium HomeostasisAntioxidants and Redox Signaling, 2010
- Selenoprotein N is required for ryanodine receptor calcium release channel activity in human and zebrafish muscleProceedings of the National Academy of Sciences of the United States of America, 2008
- Chaperone-mediated coupling of endoplasmic reticulum and mitochondrial Ca2+ channelsThe Journal of cell biology, 2006
- Selenoproteins and Their Impact on Human Health Through Diverse Physiological PathwaysPhysiology, 2006
- Structural and functional features and significance of the physical linkage between ER and mitochondriaThe Journal of cell biology, 2006
- An Integrated Stress Response Regulates Amino Acid Metabolism and Resistance to Oxidative StressMolecular Cell, 2003