Cytochrome c oxidase inhibition by N-retinyl-N-retinylidene ethanolamine, a compound suspected to cause age-related macula degeneration

H. Shaban, P. Gazzotti, C. Richter

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

The endogenous lipophilic and cationic compound N-retinyl-N-retinylidene ethanolamine (A2E) is suspected to cause age-related macula degeneration. It inhibits cytochrome c oxidase, detaches proapoptotic proteins from mitochondria, and induces apoptosis in mammalian retinal pigment epithelial cells (M. Suter, C. E. Remé, C. Grimm, A. Wenzel, M. Jäättela, P. Esser, N. Kociok, M. Leist, and C. Richter, 2000, J. Biol. Chem. 275, 39625-39630). The inhibition of cytochrome c oxidase is highly specific for A2E and is observed with the solubilized and reconstituted enzyme. In the dark, inhibition is overcome by cardiolipin or other acidic phospholipids. With illumination, inhibition is stronger, becomes complete with prolonged exposure, and is then no longer abrogated by cardiolipin. Cardiolipin effectively displaces A2E from cytochrome c oxidase, suggesting noncovalent binding of A2E to the enzyme. We conclude that A2E is a potent cytochrome c oxidase-specific inhibitor which interferes with the binding of cytochrome c to cytochrome c oxidase and, in the light, causes persistent modifications of the enzyme.

Original languageEnglish
Pages (from-to)111-116
Number of pages6
JournalArchives of Biochemistry and Biophysics
Volume394
Issue number1
DOIs
Publication statusPublished - Oct 1 2001

Keywords

  • A2E
  • Age-related macula degeneration
  • Apoptosis
  • Cardiolipin
  • Cytochrome c
  • Cytochrome c oxidase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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