April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
Positive Correlation of Prohibitin-Phospholipid to Age-Related Macular Degeneration
Author Affiliations & Notes
  • Chikaodili Emmanuel Chukwuneke
    Petroleum Chemistry, American University of Nigeria, Yola, Nigeria
  • O'Donnell Sylvester
    Petroleum Chemistry, American University of Nigeria, Yola, Nigeria
  • Srinivas Rao Sripathi
    Ophthamology, John Hopkins University, Baltimore, MD
  • Folami Lamoke
    Ophthamology, Georgia Health Science, Augusta, GA
  • Paul S Bernstein
    Ophthamology and Visual Sciences, University of Utah, Salt Lake City, UT
  • Manuela Bartoli
    Ophthamology, Georgia Health Science, Augusta, GA
  • Wan Jin Jahng
    Petroleum Chemistry, American University of Nigeria, Yola, Nigeria
  • Footnotes
    Commercial Relationships Chikaodili Chukwuneke, None; O'Donnell Sylvester, None; Srinivas Sripathi, None; Folami Lamoke, None; Paul Bernstein, None; Manuela Bartoli, None; Wan Jin Jahng, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1330. doi:
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      Chikaodili Emmanuel Chukwuneke, O'Donnell Sylvester, Srinivas Rao Sripathi, Folami Lamoke, Paul S Bernstein, Manuela Bartoli, Wan Jin Jahng; Positive Correlation of Prohibitin-Phospholipid to Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1330.

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

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Purpose: Age-related macular degeneration (AMD) involves progressive cell death of post-mitotic RPE cells. The current study examines the correlation between prohibitin as a metabolic anti-apoptotic switch with phospholipids in a stress-dependent manner. The changes of prohibitin-lipid interaction in RPE identify key elements of apoptotic networks that follow lipid metabolism and serve as a framework of biochemical pathways in AMD.

Methods: Immunoprecipitation and immunocytochemistry were performed to identify and visualize protein localization and expressions from RPE cells. Two-dimensional SDS-PAGE and Western blotting were used to identify proteins in AMD eyes compared to age-matching control. Selected spots from 2D electrophoresis were excised and analyzed by MALDI-TOF/ESI MS/MS. Lipid-prohibitin interaction assay was performed to identify prohibitin binding molecules, inlcuding cardiolipin, cholesterol and phosphatidyl inositides.

Results: Lipid-prohibitin interaction assay shows that subcellular prohibitins have different binding affinities with cardiolipin, cholesterol and phosphatidylserine. Mitochondrial prohibitin has a strong affinity at low cardiolipin concentrations (6-10 nmol). Retinal prohibitin and cardiolipin have strong binding affinity, while prohibitins from bovine RPE and human RPE cells have weaker binding affinity. Retinal microsomal prohibitin has high binding affinity with cardiolipin, cholesterol, and phosphotidylserine. Our study shows that under oxidative stress, prohibitin binds with cardiolipin whereas under normal conditions, prohibitin interacts with phosphatidylinositol triphosphate. The study demonstrated that prohibitin-lipid binding switch mediated by cardiolipin and phosphatidylinositol may control dynamic translocation of prohibitin between nucleus and the mitochondria. The results demonstrate a correlation between prohibitin-lipid interaction and AMD.

Conclusions: Mitochondrial dysfunction by prohibitin depletion is associated with AMD. The current in vivo models and molecular interaction studies, including lipid, nucleotide and protein binding assays, may provide a new insight into the underlying mechanisms involved in the development and progression of AMD and further suggest the relationship between various risk factors, such as oxidative stress, lipid environment, and aging.

Keywords: 412 age-related macular degeneration • 695 retinal degenerations: cell biology • 663 proteomics  

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