PARK2/Parkin-mediated mitochondrial clearance contributes to proteasome activation during slow-twitch muscle atrophy via NFE2L1 nuclear translocation

被引：41

作者：

Furuya, Norihiko ^{[1
]}

Ikeda, Shin-Ichi ^{[2
]}

Sato, Shigeto ^{[3
]}

Soma, Sanae ^{[1
]}

Ezaki, Junji ^{[1
]}

Trejo, Juan Alejandro Oliva ^{[1
]}

Takeda-Ezaki, Mitsue ^{[1
]}

Fujimura, Tsutomu ^{[4
]}

Arikawa-Hirasawa, Eri ^{[3
,5
]}

Tada, Norihiro ^{[5
]}

Komatsu, Masaaki ^{[6
]}

Tanaka, Keiji ^{[7
]}

Kominami, Eiki ^{[1
]}

Hattori, Nobutaka ^{[3
]}

Ueno, Takashi ^{[1
]}

机构：

[1] Juntendo Univ, Sch Med, Dept Biochem, Bunkyo Ku, Tokyo 113, Japan

[2] Juntendo Univ, Grad Sch Med, Sportol Ctr, Bunkyo Ku, Tokyo, Japan

[3] Juntendo Univ, Sch Med, Dept Neurol, Bunkyo Ku, Tokyo 113, Japan

[4] Juntendo Univ, Grad Sch Med, Lab Prote & Biomol Sci,Res Support Ctr, Bunkyo Ku, Tokyo, Japan

[5] Juntendo Univ, Grad Sch Med, Res Inst Dis Old Age, Bunkyo Ku, Tokyo, Japan

[6] Tokyo Metropolitan Inst Med Sci, Prot Metab Project, Setagaya Ku, Tokyo 113, Japan

[7] Tokyo Metropolitan Inst Med Sci, Lab Prot Metab, Setagaya Ku, Tokyo 113, Japan

来源：

AUTOPHAGY | 2014年 / 10卷 / 04期

关键词：

PARK2-mediated mitophagy; skeletal muscle atrophy; proteasome; NFE2L1; slow-twitch muscle; autophagy; mitochondria; knockout mouse; TRANSCRIPTION FACTOR NRF1; CUL3-BASED E3 LIGASE; SKELETAL-MUSCLE; ENDOPLASMIC-RETICULUM; PROTEIN-DEGRADATION; AUTOPHAGY; PARKIN; PATHWAY; SYSTEM; KEAP1;

D O I：

10.4161/auto.27785

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Skeletal muscle atrophy is thought to result from hyperactivation of intracellular protein degradation pathways, including autophagy and the ubiquitin-proteasome system. However, the precise contributions of these pathways to muscle atrophy are unclear. Here, we show that an autophagy deficiency in denervated slow-twitch soleus muscles delayed skeletal muscle atrophy, reduced mitochondrial activity, and induced oxidative stress and accumulation of PARK2/Parkin, which participates in mitochondrial quality control (PARK2-mediated mitophagy), in mitochondria. Soleus muscles from denervated Park2 knockout mice also showed resistance to denervation, reduced mitochondrial activities, and increased oxidative stress. In both autophagy-deficient and Park2-deficient soleus muscles, denervation caused the accumulation of polyubiquitinated proteins. Denervation induced proteasomal activation via NFE2L1 nuclear translocation in control mice, whereas it had little effect in autophagy-deficient and Park2-deficient mice. These results suggest that PARK2-mediated mitophagy plays an essential role in the activation of proteasomes during denervation atrophy in slow-twitch muscles.

引用

页码：631 / 641

页数：11