Myotubularin family phosphatase ceMTM3 is required for muscle maintenance by preventing excessive autophagy in Caenorhabditis elegans

BMC Cell Biology

Zhizhuang Joe Zhao²  Xueqi Fu¹  Wanke Zhao²  Feng Lin¹  Junfeng Ma¹  Xiaokun Yu¹ 

[1] Edmond H. Fischer Signal Transduction Laboratory, College of Life Sciences, Jilin University, Changchun, 130023, China;Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, 73104, USA

关键词: Sarcopenia;    C. elegans;    Muscle;    Autophagy;    RNAi;    Myotubalarin;    Phosphatase;   

Others  :  856722
DOI  :  10.1186/1471-2121-13-28

 received in 2011-12-14, accepted in 2012-10-17,  发布年份 2012

【 摘 要 】

Background

Autophagy is a ubiquitous cellular process responsible for the bulk degradation of cytoplasmic components through the autophagosomal-lysosomal pathway. In skeletal muscle, autophagy has been regarded as a key regulator for muscle mass maintenance, and its imbalance leads to sarcopenia. However, the underlying mechanism is poorly understood.

Results

In this study, we demonstrate that ceMTM3, a FYVE-domain containing myotubalarin family phosphatase, is required for the maintenance of muscle fibers by preventing excessive autophagy in Caenorhabditis elegans. Knockdown of ceMTM3 by using feeding-based RNA interference caused loss of muscle fibers accompanied by shortening of muscle cell and body size in aged C. elegans worms. This was preceded by the occurrence of excessive autophagy in the muscle and other tissues, which subsequently resulted in increased lysosomal activity and necrotic cell death. However, knockdown of ceMTM3 did not aggravate the abnormalities of muscle wasting in autophagy-deficient atg-18 mutant worms.

Conclusions

Our data suggest an important role of ceMTM3 in regulating autophagy and maintaining muscle fibers. This study may have clinical implications for prevention and treatment of sarcopenia.

【 授权许可】

   
2012 Yu et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 2.

Figure 3.

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