Mitochondria-Nucleus Communication Mediated by Prohibitin

Abstract

Purpose: : Mitochondria-nucleus communication is the central question to understand how mitochondrial activities and functions are properly maintained. Disruption of this network leads to accelerated aging and age-related diseases. Considering the consequences of mitochondrial dysfunction in age-related macular degeneration (AMD), it is crucial to understand communications between mitochondria and the nucleus at the molecular level. Our goal is to understand how mitochondria-nucleus network is adjusted for the survival of retinal and RPE cells under stress conditions.

Methods: : ARPE-19 cells were cultured under oxidative stress conditions. Biochemical techniques, including 2D electrophoresis, Western blot, immunocytochemistry, DNA-binding assay, subcellular fractionation, and lipid binding assay, were used to examine the role of prohibitin (PHB) in RPE.

Results: : Under oxidative stress, expression patterns of apoptotic and autophagic markers were altered, and these factors were translocalized between mitochondria and the nucleus, suggesting that PHB in RPE is an early marker in the apoptotic pathway. By biochemical analyses, we demonstrated that PHB binds cardiolipin, a mitochondrial specific lipid, and mitochondrial DNA, but not nuclear DNA. We further showed that PHB is translocalized from mitochondria to the nucleus, by using immunocytochemistry and Western blot.

Conclusions: : The aging animal model represents a powerful tool for exploring the pathophysiological progression of retinal degeneration. Changes in the levels of PHB and its translocalization triggered by redox imbalance are crucial for mitochondrial integrity. Our study identifies PHB as a key mediator of mitochondrial and nucleus communications under stress conditions to protect RPE from degeneration.

Keywords: proteomics • mitochondria • retinal pigment epithelium