title: Altered Cytoskeleton as a Mitochondrial Decay Signature in the Retinal Pigment Epithelium.
abstract: Mitochondria mediate energy metabolism, apoptosis, and aging, while mitochondrial disruption leads to age-related diseases that include age-related macular degeneration. Descriptions of mitochondrial morphology have been non-systematic and qualitative, due to lack of knowledge on the molecular mechanism of mitochondrial dynamics. The current study analyzed mitochondrial size, shape, and position quantitatively in retinal pigment epithelial cells (RPE) using a systematic computational model to suggest mitochondrial trafficking under oxidative environment. Our previous proteomic study suggested that prohibitin is a mitochondrial decay biomarker in the RPE. The current study examined the prohibitin interactome map using immunoprecipitation data to determine the indirect signaling on cytoskeletal changes and transcriptional regulation by prohibitin. Immunocytochemistry and immunoprecipitation demonstrated that there is a positive correlation between mitochondrial changes and altered filaments as well as prohibitin interactions with kinesin and unknown proteins in the RPE. Specific cytoskeletal and nuclear protein-binding mechanisms may exist to regulate prohibitin-mediated reactions as key elements, including vimentin and p53, to control apoptosis in mitochondria and the nucleus. Prohibitin may regulate mitochondrial trafficking through unknown proteins that include 110 kDa protein with myosin head domain and 88 kDa protein with cadherin repeat domain. Altered cytoskeleton may represent a mitochondrial decay signature in the RPE. The current study suggests that mitochondrial dynamics and cytoskeletal changes are critical for controlling mitochondrial distribution and function. Further, imbalance of retrograde versus anterograde mitochondrial trafficking may initiate the pathogenic reaction in adult-onset neurodegenerative diseases.
authors.affiliation: Department of Ophthalmology, Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Srinivas R
authors.initials: SR
authors.lastname: Sripathi
authors.affiliation: Department of Biomedical Engineering, Michigan Technological University, Houghton, MI, USA.
authors.forename: Weilue
authors.initials: W
authors.lastname: He
authors.affiliation: Retina Proteomics Laboratory, Department of Petroleum Chemistry, American University of Nigeria, Yola, Nigeria.
authors.forename: O'Donnell
authors.initials: O
authors.lastname: Sylvester
authors.affiliation: Department of Chemistry, Modibbo Adama University of Technology, Yola, Nigeria.
authors.forename: Musa
authors.initials: M
authors.lastname: Neksumi
authors.affiliation: Department of Optometry, Seoul National University of Science and Technology, Seoul, Korea.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Um
authors.affiliation: Department of Biochemistry, Modibbo Adama University of Technology, Yola, Nigeria.
authors.forename: Thagriki
authors.initials: T
authors.lastname: Dluya
authors.affiliation: Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Bernstein
authors.affiliation: Retina Proteomics Laboratory, Department of Petroleum Chemistry, American University of Nigeria, Yola, Nigeria. wan.jahng@aun.edu.ng.
authors.forename: Wan Jin
authors.initials: WJ
authors.lastname: Jahng
mesh_terms: D000818:Animals; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D063154:Mitochondrial Dynamics; D018384:Oxidative Stress; D000091402:Prohibitins; D060066:Protein Interaction Maps; D012097:Repressor Proteins / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism*
chemical_list: D000091402:Prohibitins; D012097:Repressor Proteins
keywords: Cytoskeleton; Mitochondria; Oxidative stress; Prohibitin; Protein interactome; Retinal pigment epithelium