Detalhes do Documento

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

Autor(es): Esteca, Marcos ; Severino, Matheus B. ; Silvestre, Joao G. ; Santos, Gustavo Palmeira dos ; Tamborlin, Leticia [UNESP] ; Luchessi, Augusto D. [UNESP] ; Moriscot, Anselmo S. ; Gustafsson, Asa B. ; Baptista, Igor L.

Data: 2021

Identificador Persistente: http://hdl.handle.net/11449/208937

Origem: Oasisbr

Assunto(s): satellite cells; differentiation; mitochondria; mitophagy

Descrição

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

FAEPEX-Unicamp

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.

Univ Estadual Campinas, Sch Appl Sci, Lab Cell & Tissue Biol, BR-13484350 Limeira, Brazil

Univ Sao Paulo, Inst Biomed Sci, Dept Anat, BR-05508900 Sao Paulo, Brazil

Univ Estadual Campinas, Sch Appl Sci, Lab Biotechnol, BR-13484350 Limeira, Brazil

Sao Paulo State Univ, Inst Biosci, BR-13506900 Rio Claro, Brazil

Univ Calif San Diego, Skaggs Sch Pharm & Pharmacol Sci, La Jolla, CA 92093 USA

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

Sao Paulo State Univ, Inst Biosci, BR-13506900 Rio Claro, Brazil

FAPESP: 2016/25876-4

FAPESP: 2019/016675

FAPESP: 19/12236-5

CAPES: 001

CNPq: 420265/2018-0