title: Mitochondrial-nuclear communication by prohibitin shuttling under oxidative stress.
abstract: Mitochondrial-nuclear communication is critical for maintaining mitochondrial activity under stress conditions. Adaptation of the mitochondrial-nuclear network to changes in the intracellular oxidation and reduction milieu is critical for the survival of retinal and retinal pigment epithelial (RPE) cells, in relation to their high oxygen demand and rapid metabolism. However, the generation and transmission of the mitochondrial signal to the nucleus remain elusive. Previously, our in vivo study revealed that prohibitin is upregulated in the retina, but downregulated in RPE cells in the aging and diabetic model. In this study, the functional role of prohibitin in the retina and RPE cells was examined using biochemical methods, including a lipid binding assay, two-dimensional gel electrophoresis, immunocytochemistry, Western blotting, and a knockdown approach. Protein depletion by siRNA characterized prohibitin as an anti-apoptotic molecule in mitochondria, while the lipid binding assay demonstrated subcellular communication between mitochondria and the nucleus under oxidative stress. The changes in the expression and localization of mitochondrial prohibitin triggered by reactive oxygen species are crucial for mitochondrial integrity. We propose that prohibitin shuttles between mitochondria and the nucleus as an anti-apoptotic molecule and a transcriptional regulator in a stress environment in the retina and RPE cells.
authors: Biological Sciences, Michigan Technological University, Houghton, Michigan 49931, United States.
authors: Srinivas R
authors: SR
authors: Sripathi
authors: Weilue
authors: W
authors: He
authors: Cameron L
authors: CL
authors: Atkinson
authors: Joseph J
authors: JJ
authors: Smith
authors: Zhicong
authors: Z
authors: Liu
authors: Beth M
authors: BM
authors: Elledge
authors: Wan Jin
authors: WJ
authors: Jahng
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D002308:Cardiolipins / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D000091402:Prohibitins; D012097:Repressor Proteins / Q000502:physiology*; D012160:Retina / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D002308:Cardiolipins; D000091402:Prohibitins; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53; D006861:Hydrogen Peroxide