Cardiac autophagic vacuolation in severe X-linked myopathy with excessive autophagy

Iulia Munteanu, Hannu Kalimo, Antti Saraste, Ichizo Nishino, Berge A. Minassian

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


X-linked myopathy with excessive autophagy (XMEA), caused by mutations of the VMA21 gene, is a strictly skeletal muscle disease. Extensive studies in yeast established VMA21 as the master assembly chaperone of V-ATPase, the complex multisubunit proton pump that acidifies organelles and that is vital to all mammalian tissues. As such, skeletal muscle disease exclusivity in XMEA is highly surprising. We now show that the severest VMA21 mutation, c.164-6t>g, does result in XMEA-typical pathology with autophagic vacuolar changes outside skeletal muscle, namely in the heart. However, even patients with this mutation do not exhibit clinical extramuscular disease, including cardiac disease, despite extreme skeletal muscle wasting to the extent of ventilation dependence. Uncovering the unique skeletal muscle vulnerability to defective organellar acidification, and resultant tissue-destructive excessive autophagy, will be informative to the understanding of muscle physiology. Alternatively, understanding extramuscular resistance to VMA21 mutation might disclose heretofore unknown mammalian V-ATPase assembly chaperones other than VMA21.

Original languageEnglish (US)
Pages (from-to)185-187
Number of pages3
JournalNeuromuscular Disorders
Issue number2
StatePublished - Feb 1 2017


  • Acidification
  • Autophagy
  • CAVM
  • Congenital
  • LAMP2
  • Lysosome
  • XMEA

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neurology
  • Clinical Neurology
  • Genetics(clinical)


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