title: Autophagy and mitophagy participate in ocular lens organelle degradation.
abstract: The eye lens consists of a layer of epithelial cells that overlay a series of differentiating fiber cells that upon maturation lose their mitochondria, nuclei and other organelles. Lens transparency relies on the metabolic function of mitochondria contained in the lens epithelial cells and in the immature fiber cells and the programmed degradation of mitochondria and other organelles occurring upon lens fiber cell maturation. Loss of lens mitochondrial function in the epithelium or failure to degrade mitochondria and other organelles in lens fiber cells results in lens cataract formation. To date, the mechanisms that govern the maintenance of mitochondria in the lens and the degradation of mitochondria during programmed lens fiber cell maturation have not been fully elucidated. Here, we demonstrate using electron microscopy and dual-label confocal imaging the presence of autophagic vesicles containing mitochondria in lens epithelial cells, immature lens fiber cells and during early stages of lens fiber cell differentiation. We also show that mitophagy is induced in primary lens epithelial cells upon serum starvation. These data provide evidence that autophagy occurs throughout the lens and that mitophagy functions in the lens to remove damaged mitochondria from the lens epithelium and to degrade mitochondria in the differentiating lens fiber cells for lens development. The results provide a novel mechanism for how mitochondria are maintained to preserve lens metabolic function and how mitochondria are degraded upon lens fiber cell maturation.
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC.
authors.forename: M Joseph
authors.initials: MJ
authors.lastname: Costello
authors.affiliation: Department of Biomedical Science, Florida Atlantic University, Boca Raton, FL.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Brennan
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University.
authors.forename: Subharsee
authors.initials: S
authors.lastname: Basu
authors.affiliation: Department of Biomedical Science, Florida Atlantic University, Boca Raton, FL.
authors.forename: Daniel
authors.initials: D
authors.lastname: Chauss
authors.affiliation: Prof. Brien Holden Eye Research Centre, L V Prasad Eye Institute, Hyderabad, India.
authors.forename: Ashik
authors.initials: A
authors.lastname: Mohamed
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC.
authors.forename: Kurt O
authors.initials: KO
authors.lastname: Gilliland
authors.affiliation: Biology Department, Duke University, Durham, NC.
authors.forename: Sönke
authors.initials: S
authors.lastname: Johnsen
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University.
authors.forename: Sue
authors.initials: S
authors.lastname: Menko
authors.affiliation: Department of Biomedical Science, Florida Atlantic University, Boca Raton, FL.
authors.forename: Marc
authors.initials: M
authors.lastname: Kantorow
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001343:Autophagy; D002386:Cataract / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D002642:Chick Embryo; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism / Q000648:ultrastructure*; D008854:Microscopy, Electron; D008875:Middle Aged; D063306:Mitophagy; D015388:Organelles / Q000648:ultrastructure*; D055815:Young Adult
keywords: ATG5; FYCO1; FYVE and coiled coil domain containing 1; LC3B; OFZ; Pik3c3; TOM20; autophagy; autophagy-related 5; cataract; differentiation; electron microscopy; lens; microtubule-associated protein 1 light chain 3B; mitophagy; organelle free zone; phosphatidylinositol 3-kinase, catalytic subunit type 3; translocase of the outer mitochondrial membranes 20 kDa