BAG6 deficiency induces mis-distribution of mitochondrial clusters under depolarization

FEBS Open Bio. 2019 Jul;9(7):1281-1291. doi: 10.1002/2211-5463.12677. Epub 2019 Jun 4.

Abstract

Accumulation of damaged mitochondria is implicated in a number of neurodegenerative disorders, including Parkinson's disease. Therefore, the machinery for mitochondrial quality control is important for the prevention of such diseases. It has been reported that Parkin- and p62/sequestosome 1 (SQSTM1)-mediated clustering and subsequent elimination of damaged mitochondria (termed mitophagy) are critical for maintaining the quality of mitochondria under stress induced by uncoupling agents such as carbonyl cyanide m-chlorophenyl hydrazone. However, the molecular mechanisms underlying mitochondrial translocation to the perinuclear region during mitophagy have not been adequately addressed to date. In this study, we found that BCL2-associated athanogene 6 (BAG6; also known as BAT3 or Scythe) is required for this process. Indeed, RNA interference-mediated depletion of endogenous BAG6 prevented Parkin-dependent relocalization of mitochondrial clusters to the perinuclear cytoplasmic region, whereas BAG6 knockdown did not affect the translocation of Parkin and p62/SQSTM1 to the depolarized mitochondria and subsequent aggregation. These results suggest that BAG6 is essential for cytoplasmic redistribution, but not for clustering, of damaged mitochondria.

Keywords: BAG6; CCCP; PINK1; Parkin; mitochondria; p62.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Autophagy / drug effects
  • Cytosol / metabolism
  • HeLa Cells
  • Humans
  • Mitochondria / metabolism*
  • Mitophagy / physiology*
  • Molecular Chaperones / genetics*
  • Molecular Chaperones / metabolism
  • Sequestosome-1 Protein / metabolism
  • Sequestosome-1 Protein / physiology
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination / drug effects

Substances

  • Adaptor Proteins, Signal Transducing
  • BAG6 protein, human
  • Molecular Chaperones
  • SQSTM1 protein, human
  • Sequestosome-1 Protein
  • Ubiquitin-Protein Ligases
  • parkin protein

Associated data

  • GENBANK/169790968