Abstract
AbstractSarcopenia is characterized by a progressive reduction in muscle mass or muscle physiological function associated with aging, but the relevant molecular mechanisms are not clear. Here, we identify the role of the myogenesis modifier CPNE1 in sarcopenia. CPNE1 is upregulated in aged skeletal muscles and young skeletal muscle satellite cells with palmitate-induced atrophy. The overexpression of CPNE1 hinders proliferation and differentiation and increases muscle atrophy characteristics in young skeletal muscle-derived satellite cells. In addition, CPNE1 overexpression disrupts the balance of mitochondrial fusion and division and causes endoplasmic reticulum stress. We found that the effects of CPNE1 on mitochondrial function are dependent on the PERK/eIF2α/ATF4 pathway. The overexpression of CPNE1 in young muscles alters membrane lipid composition, reduces skeletal muscle fibrosis regeneration, and exercise capacity in mice. These effects were reversed by PERK inhibitor GSK2606414. Moreover, immunoprecipitation indicates that CPNE1 overexpression greatly increased the acetylation of PERK. Therefore, CPNE1 is an important modifier that drives mitochondrial homeostasis to regulate myogenic cell proliferation and differentiation via the PERK-eIF2α pathway, which could be a valuable target for age-related sarcopenia.
Funder
Aging and Women and Children's Health Research Project of Shanghai Municipality
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Histology,Pathology and Forensic Medicine
Reference48 articles.
1. Annunziata C, Jordan N, David T, Amandine, (2018) Oxidative muscles have better mitochondrial homeostasis than glycolytic muscles throughout life and maintain mitochondrial function during aging. Aging 10:3327–3352
2. Azarova I, Klyosova E, Polonikov A (2021) The link of type 2 diabetes mellitus to the polymorphisms of glutathione-metabolizing genes suggests a new hypothesis explaining disease initiation and progression. Life (Basel, Switzerland) 11:9
3. Barreiro E, Salazar-Degracia A, Sancho-Muñoz A, Gea J (2019) Endoplasmic reticulum stress and unfolded protein response profile in quadriceps of sarcopenic patients with respiratory diseases. J Cell Physiol 234:11315–11329
4. Bazgir B, Fathi R, Valojerdi MR, Mozdziak P, Asgari A (2017) Satellite cells contribution to exercise mediated muscle hypertrophy and repair. Cell 18:473–484
5. Bentzinger C, Wang Y, Rudnicki M (2012) Building muscle: molecular regulation of myogenesis. Cold Spring Harb Perspect Biol 4:2
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