title: Myotubularin family phosphatase ceMTM3 is required for muscle maintenance by preventing excessive autophagy in Caenorhabditis elegans.
abstract: 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.
authors.affiliation: Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, 73104, USA.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Yu
authors.forename: Junfeng
authors.initials: J
authors.lastname: Ma
authors.forename: Feng
authors.initials: F
authors.lastname: Lin
authors.forename: Wanke
authors.initials: W
authors.lastname: Zhao
authors.forename: Xueqi
authors.initials: X
authors.lastname: Fu
authors.forename: Zhizhuang Joe
authors.initials: ZJ
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001343:Autophagy; D049628:Body Size; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D009154:Mutation; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D054558:Protein Tyrosine Phosphatases, Non-Receptor; C532246:mtm-3 protein, C elegans