Loss of Parkin impairs mitochondrial function and leads to muscle atrophy.

Peker, Nesibe, Donipadi, Vinay, Sharma, Mridula, McFarlane, Craig, and Kambadur, Ravi (2018) Loss of Parkin impairs mitochondrial function and leads to muscle atrophy. American Journal of Physiology: cell physiology, 315 (2). C164-C185.

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Abstract

Parkinson's Disease is a neurodegenerative disease characterized by tremors, muscle stiffness and muscle weakness. Molecular genetic analysis confirmed that mutations in PARKIN and PINK1 genes, which play major roles in mitochondrial quality control and mitophagy, are frequently associated with Parkinson's Disease. PARKIN is an E3 ubiquitin ligase that translocates to mitochondria during loss of mitochondrial membrane potential to increase mitophagy. Although muscle dysfunction is noted in Parkinson's Disease, little is known about the involvement of PARKIN in the muscle phenotype of Parkinson's Disease. In this study, we report that the mitochondrial uncoupler CCCP promotes PINK1/PARKIN-mediated mitophagy in myogenic C2C12 cells. As a result of this excess mitophagy, we show that CCCP treatment of myotubes leads to the development of myotube atrophy in vitro. Surprisingly, we also found that siRNA-mediated knock down of Parkin results in accumulation of dysfunctional mitochondria, possibly due to impaired mitochondrial turnover. In addition, knock down of Parkin led to myotubular atrophy in vitro. Consistent with these in vitro results, Parkin knockout muscles showed impaired mitochondrial function and smaller myofiber area, suggesting that Parkin function is required for post-natal skeletal muscle growth and development.

Item ID: 53604
Item Type: Article (Research - C1)
ISSN: 1522-1563
Keywords: Parkin; atrophy; mitochondria; mitochondrial turnover; skeletal muscle
Copyright Information: Copyright © 2018 the American Physiological Society
Funders: Agency for Science Technology and Research (A*STAR), Singapore, Turkish Education Foundation, Singapore International Graduate Student Award
Date Deposited: 01 Oct 2018 23:57
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060104 Cell Metabolism @ 70%
06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060103 Cell Development, Proliferation and Death @ 30%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 80%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920112 Neurodegenerative Disorders Related to Ageing @ 20%
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