June 2020
Volume 61, Issue 7
ARVO Annual Meeting Abstract  |   June 2020
Author Affiliations & Notes
  • Srimal Samaranayake
    Pharmacology, Vanderbilt University, Nashville, Tennessee, United States
  • Sergey A Vishnivetskiy
    Pharmacology, Vanderbilt University, Nashville, Tennessee, United States
  • Eugenia V Gurevich
    Pharmacology, Vanderbilt University, Nashville, Tennessee, United States
  • Vsevolod V Gurevich
    Pharmacology, Vanderbilt University, Nashville, Tennessee, United States
  • Footnotes
    Commercial Relationships   Srimal Samaranayake, None; Sergey Vishnivetskiy, None; Eugenia Gurevich, None; Vsevolod Gurevich, None
  • Footnotes
    Support  EY011500
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 1521. doi:
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      Srimal Samaranayake, Sergey A Vishnivetskiy, Eugenia V Gurevich, Vsevolod V Gurevich; THE EFFECT OF ARRESTIN-1 SELF-ASSOCIATION ON ROD MITOCHONDRIA. Invest. Ophthalmol. Vis. Sci. 2020;61(7):1521.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : To test the biological role of arrestin-1 self-association in mitochondria.

Methods : Several transgenic mouse lines that express arrestin-1 mutant deficient in self-association were created on arrestin-1 knockout (AKO) background. The lowest and highest transgene expression ranged from 77% to 292% relative to wild type (WT) level. Rod mitochondrial morphology was characterized using images collected from tunneling electron microscopy (TEM).

Results : We previously found that high expression (292%) of non-oligomerizing arrestin-1 mutant induces degeneration of rod photoreceptors. In contrast, lower expression (77%) was not harmful. To determine the role of arrestin-1 self-association, we used two transgenic lines expressing the highest (292% - M5) and the lowest (77% -M10) (relative to WT) levels of arrestin-1 that carried mutations selectively preventing its self-association. The mouse lines expressing the mutant arrestin-1 demonstrated significant alterations in the morphology of the rod photoreceptor mitochondria. The mitochondria in the M5 line were enlarged as compared to WT, round in shape, and pale in appearance. The M10 line showed similar morphology, albeit less pronounced. Thus, the higher expressor M5 showed reduced major axis dimensions and increased minor axis dimensions of mitochondria, resulting in lower major/minor axis ratio (~ 1) relative to WT and arrestin-1 knockout (AKO) rod mitochondria. M5 also demonstrated higher mitochondrial surface area, as compared to other mouse lines. Additionally, rod mitochondria of M5 line had lower optical density and reduced number of cristae, as compared to WT and AKO lines. The lower expressor M10 showed quantitatively less pronounced but qualitatively similar morphological changes to that in M5.

Conclusions : High expression of self-association-deficient arrestin-1 damaged rod mitochondria, suggesting that arrestin-1 oligomerizes to prevent cytotoxicity of the monomer to mitochondria, thereby preserving photoreceptor health.

This is a 2020 ARVO Annual Meeting abstract.


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