Optineurin E50K triggers BDNF deficiency-mediated mitochondrial dysfunction in retinal photoreceptor cell line

Biochem Biophys Res Commun. 2018 Sep 18;503(4):2690-2697. doi: 10.1016/j.bbrc.2018.08.025. Epub 2018 Aug 9.

Abstract

Optineurin (OPTN) mutations are linked to glaucoma pathology and E50K mutation shows massive cell death in photoreceptor cells and retinal ganglion cells. However, little is known about E50K-mediated mitochondrial dysfunction in photoreceptor cell degeneration. We here show that overexpression of E50K expression triggered BDNF deficiency, leading to Bax activation in RGC-5 cells. BDNF deficiency induced mitochondrial dysfunction by decreasing mitochondrial maximal respiration and reducing intracellular ATP level in RGC-5 cells. However, BDNF deficiency did not alter mitochondrial dynamics. Also, BDNF deficiency resulted in LC3-mediated mitophagosome formation in RGC-5 cells. These results strongly suggest that E50K-mediated BDNF deficiency plays a critical role in compromised mitochondrial function in glaucomatous photoreceptor cell degeneration.

Keywords: BDNF; E50K mutation; Glaucoma; Mitochondrial dysfunction; Optineurin; RGC-5 cell.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphate / biosynthesis
  • Amino Acid Substitution
  • Animals
  • Brain-Derived Neurotrophic Factor / deficiency
  • Brain-Derived Neurotrophic Factor / genetics*
  • Cell Line
  • Gene Expression Regulation
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Mitochondria / metabolism*
  • Mitochondria / pathology
  • Mutation
  • Oxidative Phosphorylation
  • Phagosomes / metabolism
  • Phagosomes / pathology
  • Photoreceptor Cells, Vertebrate / metabolism*
  • Photoreceptor Cells, Vertebrate / pathology
  • Rats
  • Signal Transduction
  • Transcription Factor TFIIIA / genetics*
  • Transcription Factor TFIIIA / metabolism
  • bcl-2-Associated X Protein / genetics*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Bax protein, rat
  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • LC3 protein, rat
  • Microtubule-Associated Proteins
  • OPTN protein, rat
  • Transcription Factor TFIIIA
  • bcl-2-Associated X Protein
  • Adenosine Triphosphate