Loss of Parkin Results in Altered Muscle Stem Cell Differentiation during Regeneration

Author(s)

Esteca, V, Marcos ; Severino, Matheus B. ^[1] ; Silvestre, Joao G. ^[2] ; dos Santos, Gustavo Palmeira ^[1] ; Tamborlin, Leticia ^{[3, 4]} ; Luchessi, Augusto D. ^{[3, 4]} ; Moriscot, Anselmo S. ^[2] ; Gustafsson, Asa B. ^[5] ; Baptista, Igor L. ^{[1, 6]}

Affiliation

^[1] Esteca, Marcos, V, Univ Estadual Campinas, Sch Appl Sci, Lab Cell & Tissue Biol, BR-13484350 Limeira - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05508900 Sao Paulo - Brazil

^[3] Univ Estadual Campinas, Sch Appl Sci, Lab Biotechnol, BR-13484350 Limeira - Brazil

^[4] Sao Paulo State Univ, Inst Biosci, BR-13506900 Rio Claro - Brazil

^[5] Univ Calif San Diego, Skaggs Sch Pharm & Pharmacol Sci, La Jolla, CA 92093 - USA

^[6] Univ Estadual Campinas, Sch Appl Sci, Rua Pedro Zaccaria 1300, BR-13484350 Limeira - Brazil

• Document type: Journal article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 21, n. 21 NOV 2020.
• Web of Science Citations: 0

Abstract

The high capacity of the skeletal muscle to regenerate is due to the presence of muscle stem cells (MuSCs, or satellite cells). The E3 ubiquitin ligase Parkin is a key regulator of mitophagy and is recruited to mitochondria during differentiation of mouse myoblast cell line. However, the function of mitophagy during regeneration has not been investigated in vivo. Here, we have utilized Parkin deficient (Parkin(-/-)) mice to investigate the role of Parkin in skeletal muscle regeneration. We found a persistent deficiency in skeletal muscle regeneration in Parkin(-/-) mice after cardiotoxin (CTX) injury with increased area of fibrosis and decreased cross-sectional area (CSA) of myofibres post-injury. There was also a significant modulation of MuSCs differentiation and mitophagic markers, with altered mitochondrial proteins during skeletal muscle regeneration in Parkin(-/-) mice. Our data suggest that Parkin-mediated mitophagy plays a key role in skeletal muscle regeneration and is necessary for MuSCs differentiation. (AU)

• FAPESP's process: 16/25876-4 - Role of Parkin on skeletal muscle adaptive response during regeneration
• Grantee: Igor Luchini Baptista
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/12236-5 - Effects of caffeine exposure on mitophagic pathways: actions over myogenic progenitor cells differentiation
• Grantee: Igor Luchini Baptista
• Support Opportunities: Regular Research Grants