Copper mediates mitochondrial biogenesis in retinal pigment epithelial cells

Biochim Biophys Acta Mol Basis Dis. 2020 Oct 1;1866(10):165843. doi: 10.1016/j.bbadis.2020.165843. Epub 2020 May 23.

Abstract

Age related macular degeneration (AMD) is a multifactorial disease with genetic, biochemical and environmental risk factors. We observed a significant increase in copper levels in choroid-RPE from donor eyeballs with AMD. Adult retinal pigment epithelial cells (ARPE19 cells) exposed to copper in-vitro showed a 2-fold increase in copper influx transporter CTR1 and copper uptake at 50 μM concentration. Further there was 2-fold increase in cytochrome C oxidase activity and a 2-fold increase in the mRNA expression of NRF 2 with copper treatment. There was a significant increase in mitochondrial biogenesis markers PGC1β and TFAM which was confirmed by mitochondrial mass and copy number. On the contrary, in AMD choroid-RPE, the CTR1 mRNA was found to be significantly down-regulated compared to its respective controls. SCO1 and PGC1β mRNA showed an increase in choroid-RPE. Our study proposes copper to play an important role in mitochondrial biogenesis in RPE cells.

Keywords: AMD; Copper; Mitochondrial biogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cell Line
  • Choroid / metabolism
  • Copper / metabolism*
  • Copper / pharmacology
  • Copper Transporter 1 / metabolism
  • DNA-Binding Proteins / metabolism
  • Electron Transport Complex IV / metabolism
  • Epithelial Cells / metabolism*
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Macular Degeneration / metabolism*
  • Macular Degeneration / pathology
  • Male
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / metabolism
  • Molecular Chaperones / metabolism
  • NF-E2-Related Factor 2 / metabolism
  • Organelle Biogenesis*
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism
  • Reactive Oxygen Species / metabolism
  • Retinal Pigment Epithelium / metabolism*
  • Retinal Pigment Epithelium / pathology
  • Retinal Pigments / genetics
  • Retinal Pigments / metabolism*
  • Transcription Factors / metabolism

Substances

  • Copper Transporter 1
  • DNA-Binding Proteins
  • Mitochondrial Proteins
  • Molecular Chaperones
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • PPARGC1B protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • Reactive Oxygen Species
  • Retinal Pigments
  • SCO1 protein, human
  • SLC31A1 protein, human
  • TFAM protein, human
  • Transcription Factors
  • Copper
  • Electron Transport Complex IV