Calcium and Redox Liaison: A Key Role of Selenoprotein N in Skeletal Muscle

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 cal...

Descripción completa

Detalles Bibliográficos
Autores principales: Zito, Ester, Ferreiro, Ana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148124/
https://www.ncbi.nlm.nih.gov/pubmed/34066362
http://dx.doi.org/10.3390/cells10051116
_version_ 1783697782845997056
author Zito, Ester
Ferreiro, Ana
author_facet Zito, Ester
Ferreiro, Ana
author_sort Zito, Ester
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8148124
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-81481242021-05-26 Calcium and Redox Liaison: A Key Role of Selenoprotein N in Skeletal Muscle Zito, Ester Ferreiro, Ana Cells Review 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. MDPI 2021-05-06 /pmc/articles/PMC8148124/ /pubmed/34066362 http://dx.doi.org/10.3390/cells10051116 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Zito, Ester
Ferreiro, Ana
Calcium and Redox Liaison: A Key Role of Selenoprotein N in Skeletal Muscle
title Calcium and Redox Liaison: A Key Role of Selenoprotein N in Skeletal Muscle
title_full Calcium and Redox Liaison: A Key Role of Selenoprotein N in Skeletal Muscle
title_fullStr Calcium and Redox Liaison: A Key Role of Selenoprotein N in Skeletal Muscle
title_full_unstemmed Calcium and Redox Liaison: A Key Role of Selenoprotein N in Skeletal Muscle
title_short Calcium and Redox Liaison: A Key Role of Selenoprotein N in Skeletal Muscle
title_sort calcium and redox liaison: a key role of selenoprotein n in skeletal muscle
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148124/
https://www.ncbi.nlm.nih.gov/pubmed/34066362
http://dx.doi.org/10.3390/cells10051116
work_keys_str_mv AT zitoester calciumandredoxliaisonakeyroleofselenoproteinninskeletalmuscle
AT ferreiroana calciumandredoxliaisonakeyroleofselenoproteinninskeletalmuscle