Copper mediates mitochondrial biogenesis in retinal pigment epithelial cells

M. Aloysius Dhivya, S. Aberami, Sampath Nikhalashree, J. Biswas, Wenjie Liu, Joseph Irudayaraj, K. N. Sulochana, Karunakaran Coral, S. R. Bharathi Devi

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number165843
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1866
Issue number10
DOIs
StatePublished - Oct 1 2020

Keywords

  • AMD
  • Copper
  • Mitochondrial biogenesis

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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  • Cite this

    Aloysius Dhivya, M., Aberami, S., Nikhalashree, S., Biswas, J., Liu, W., Irudayaraj, J., Sulochana, K. N., Coral, K., & Bharathi Devi, S. R. (2020). Copper mediates mitochondrial biogenesis in retinal pigment epithelial cells. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1866(10), [165843]. https://doi.org/10.1016/j.bbadis.2020.165843