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

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2020 Oct 31

PMID 33126429

Citations 11

Authors

Marcos V Esteca

Matheus B Severino

Joao G Silvestre

Gustavo Palmeira Dos Santos

Leticia Tamborlin

Augusto D Luchessi

Anselmo S Moriscot

Asa B Gustafsson

Igor L Baptista

Affiliations

Soon will be listed here.

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.

Citing Articles

Alterations of PINK1-PRKN signaling in mice during normal aging.

Baninameh Z, Watzlawik J, Hou X, Richardson T, Kurchaba N, Yan T Autophagy Rep. 2025; 3(1).

PMID: 40008113 PMC: 11855339. DOI: 10.1080/27694127.2024.2434379.

Transcriptional regulation of autophagy in skeletal muscle stem cells.

Gopal Krishnan P, Lee W, Goh K, Choy S, Turqueza L, Lim Z Dis Model Mech. 2025; 18(2).

PMID: 39925192 PMC: 11849978. DOI: 10.1242/dmm.052007.

Ubiquitination Insight from Spinal Muscular Atrophy-From Pathogenesis to Therapy: A Muscle Perspective.

Bolado-Carrancio A, Tapia O, Rodriguez-Rey J Int J Mol Sci. 2024; 25(16).

PMID: 39201486 PMC: 11354275. DOI: 10.3390/ijms25168800.

Mitophagy in fibrotic diseases: molecular mechanisms and therapeutic applications.

Cui X, Zhou Z, Tu H, Wu J, Zhou J, Yi Q Front Physiol. 2024; 15:1430230.

PMID: 39183973 PMC: 11341310. DOI: 10.3389/fphys.2024.1430230.

Crosstalk of ubiquitin system and non-coding RNA in fibrosis.

Zhang H, Zhou Y, Jiang C, Jian N, Wang J Int J Biol Sci. 2024; 20(10):3802-3822.

PMID: 39113708 PMC: 11302871. DOI: 10.7150/ijbs.93644.

References

Wen Y, Bi P, Liu W, Asakura A, Keller C, Kuang S . Constitutive Notch activation upregulates Pax7 and promotes the self-renewal of skeletal muscle satellite cells. Mol Cell Biol. 2012; 32(12):2300-11. PMC: 3372272. DOI: 10.1128/MCB.06753-11. View

Schmidt M, Schuler S, Huttner S, von Eyss B, von Maltzahn J . Adult stem cells at work: regenerating skeletal muscle. Cell Mol Life Sci. 2019; 76(13):2559-2570. PMC: 6586695. DOI: 10.1007/s00018-019-03093-6. View

Lampert M, Orogo A, Najor R, Hammerling B, Leon L, Wang B . BNIP3L/NIX and FUNDC1-mediated mitophagy is required for mitochondrial network remodeling during cardiac progenitor cell differentiation. Autophagy. 2019; 15(7):1182-1198. PMC: 6613840. DOI: 10.1080/15548627.2019.1580095. View

Mahdy M, Warita K, Hosaka Y . Early ultrastructural events of skeletal muscle damage following cardiotoxin-induced injury and glycerol-induced injury. Micron. 2016; 91:29-40. DOI: 10.1016/j.micron.2016.09.009. View

Olguin H, Pisconti A . Marking the tempo for myogenesis: Pax7 and the regulation of muscle stem cell fate decisions. J Cell Mol Med. 2011; 16(5):1013-25. PMC: 4365881. DOI: 10.1111/j.1582-4934.2011.01348.x. View

Rocheteau P, Gayraud-Morel B, Siegl-Cachedenier I, Blasco M, Tajbakhsh S . A subpopulation of adult skeletal muscle stem cells retains all template DNA strands after cell division. Cell. 2012; 148(1-2):112-25. DOI: 10.1016/j.cell.2011.11.049. View

Pinto M, Nissanka N, Moraes C . Lack of Parkin Anticipates the Phenotype and Affects Mitochondrial Morphology and mtDNA Levels in a Mouse Model of Parkinson's Disease. J Neurosci. 2017; 38(4):1042-1053. PMC: 5783961. DOI: 10.1523/JNEUROSCI.1384-17.2017. View

Zhang K, Zhang Y, Gu L, Lan M, Liu C, Wang M . Islr regulates canonical Wnt signaling-mediated skeletal muscle regeneration by stabilizing Dishevelled-2 and preventing autophagy. Nat Commun. 2018; 9(1):5129. PMC: 6277414. DOI: 10.1038/s41467-018-07638-4. View

Chen C, Erlich A, Crilly M, Hood D . Parkin is required for exercise-induced mitophagy in muscle: impact of aging. Am J Physiol Endocrinol Metab. 2018; 315(3):E404-E415. DOI: 10.1152/ajpendo.00391.2017. View

10.

Romanello V, Sandri M . Mitochondrial Quality Control and Muscle Mass Maintenance. Front Physiol. 2016; 6:422. PMC: 4709858. DOI: 10.3389/fphys.2015.00422. View

11.

Sin J, Andres A, Taylor D, Weston T, Hiraumi Y, Stotland A . Mitophagy is required for mitochondrial biogenesis and myogenic differentiation of C2C12 myoblasts. Autophagy. 2015; 12(2):369-80. PMC: 4836019. DOI: 10.1080/15548627.2015.1115172. View

12.

Murphy M, Keefe A, Lawson J, Flygare S, Yandell M, Kardon G . Transiently active Wnt/β-catenin signaling is not required but must be silenced for stem cell function during muscle regeneration. Stem Cell Reports. 2014; 3(3):475-88. PMC: 4266007. DOI: 10.1016/j.stemcr.2014.06.019. View

13.

Schiaffino S, Rossi A, Smerdu V, Leinwand L, Reggiani C . Developmental myosins: expression patterns and functional significance. Skelet Muscle. 2015; 5:22. PMC: 4502549. DOI: 10.1186/s13395-015-0046-6. View

14.

Servian-Morilla E, Cabrera-Serrano M, Rivas-Infante E, Carvajal A, Lamont P, Pelayo-Negro A . Altered myogenesis and premature senescence underlie human TRIM32-related myopathy. Acta Neuropathol Commun. 2019; 7(1):30. PMC: 6396567. DOI: 10.1186/s40478-019-0683-9. View

15.

Gouspillou G, Godin R, Piquereau J, Picard M, Mofarrahi M, Mathew J . Protective role of Parkin in skeletal muscle contractile and mitochondrial function. J Physiol. 2018; 596(13):2565-2579. PMC: 6023825. DOI: 10.1113/JP275604. View

16.

Rana A, Rera M, Walker D . Parkin overexpression during aging reduces proteotoxicity, alters mitochondrial dynamics, and extends lifespan. Proc Natl Acad Sci U S A. 2013; 110(21):8638-43. PMC: 3666724. DOI: 10.1073/pnas.1216197110. View

17.

Kubli D, Zhang X, Lee Y, Hanna R, Quinsay M, Nguyen C . Parkin protein deficiency exacerbates cardiac injury and reduces survival following myocardial infarction. J Biol Chem. 2012; 288(2):915-26. PMC: 3543040. DOI: 10.1074/jbc.M112.411363. View

18.

Stevens-Lapsley J, Kluger B, Schenkman M . Quadriceps muscle weakness, activation deficits, and fatigue with Parkinson disease. Neurorehabil Neural Repair. 2011; 26(5):533-41. DOI: 10.1177/1545968311425925. View

19.

Baldelli S, Aquilano K, Ciriolo M . PGC-1α buffers ROS-mediated removal of mitochondria during myogenesis. Cell Death Dis. 2014; 5:e1515. PMC: 4260723. DOI: 10.1038/cddis.2014.458. View

20.

Bhattacharya D, Scime A . Mitochondrial Function in Muscle Stem Cell Fates. Front Cell Dev Biol. 2020; 8:480. PMC: 7308489. DOI: 10.3389/fcell.2020.00480. View