title: Mitochondrial Fission Increases Apoptosis and Decreases Autophagy in Renal Proximal Tubular Epithelial Cells Treated with High Glucose.
abstract: The aim of this study was to examine the effect of mitochondrial morphogenesis changes on apoptosis and autophagy of high-glucose-treated proximal tubular epithelial cells (HK2). Cell viability, apoptosis, and mitochondrial morphogenesis were examined using crystal violet, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and mitotracker staining, respectively. High glucose inhibited cell viability and induced mitochondrial fission in HK2 cells. After depleting mitofusin 1 (MFN1), the MFN1(-) HK2 cells (fission type) became more susceptible to high-glucose-induced apoptosis and mitochondrial fragmentation observed by TUNEL and mitotracker assays. In siMFN2 HK2 cells (fission type), mitochondria were highly fragmented (>80% fission rate) with or without high-glucose treatment; however, siFIS1 (mitochondrial fission protein 1) HK2 cells (fusion type) exhibited little fragmentation (<13%). High-glucose treatment induced autophagy, characterized by the formation of autophagosome and microtubule-associated protein light chain 3 (LC3) B-II, as observed by transmission electron microscopy and western blotting, respectively. LC3B-II levels decreased in both MFN1(-) and siMFN2 HK2 cells, but increased in siFIS1 HK2 cells. Moreover, autophagy displays a protective role against high-glucose-induced cell death based on cotreatment with autophagy inhibitors (3-methyladenine and chloroquine). Mitochondrial fission may increase apoptosis and decrease autophagy of high-glucose-treated HK2 cells.
authors.affiliation: 1 Mitochondrial Research Unit, Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine , Kaohsiung, Taiwan .
authors.forename: Wen-Chin
authors.initials: WC
authors.lastname: Lee
authors.affiliation: 1 Mitochondrial Research Unit, Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine , Kaohsiung, Taiwan .
authors.forename: Chien-Hua
authors.initials: CH
authors.lastname: Chiu
authors.affiliation: 1 Mitochondrial Research Unit, Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine , Kaohsiung, Taiwan .
authors.forename: Jin-Bor
authors.initials: JB
authors.lastname: Chen
authors.affiliation: 1 Mitochondrial Research Unit, Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine , Kaohsiung, Taiwan .|2 Department of Biological Sciences, National Sun Yat-Sen University , Kaohsiung, Taiwan .
authors.forename: Chiu-Hua
authors.initials: CH
authors.lastname: Chen
authors.affiliation: 3 Institute of Medical Science and Technology, National Sun Yat-Sen University , Kaohsiung, Taiwan .|4 Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University , Kaohsiung, Taiwan .
authors.forename: Hsueh-Wei
authors.initials: HW
authors.lastname: Chang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000187:drug effects
chemical_list: D008869:Microtubule-Associated Proteins; D005947:Glucose
keywords: apoptosis; autophagy; high glucose; mitochondrial fission; renal HK2 cells