title: Molecular identity of cardiac mitochondrial chloride intracellular channel proteins.
abstract: Emerging evidences demonstrate significance of chloride channels in cardiac function and cardioprotection from ischemia-reperfusion (IR) injury. Unlike mitochondrial potassium channels sensitive to calcium (BKCa) and ATP (KATP), molecular identity of majority of cardiac mitochondrial chloride channels located at the inner membrane is not known. In this study, we report the presence of unique dimorphic chloride intracellular channel (CLIC) proteins namely CLIC1, CLIC4 and CLIC5 as abundant CLICs in the rodent heart. Further, CLIC4, CLIC5, and an ortholog present in Drosophila (DmCLIC) localize to adult cardiac mitochondria. We found that CLIC4 is enriched in the outer mitochondrial membrane, whereas CLIC5 is present in the inner mitochondrial membrane. Also, CLIC5 plays a direct role in regulating mitochondrial reactive oxygen species (ROS) generation. Our study highlights that CLIC5 is localized to the cardiac mitochondria and directly modulates mitochondrial function.
authors.affiliation: Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, United States.
authors.forename: Devasena
authors.initials: D
authors.lastname: Ponnalagu
authors.affiliation: Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, United States.
authors.forename: Shubha
authors.initials: S
authors.lastname: Gururaja Rao
authors.affiliation: Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, United States.
authors.forename: Jason
authors.initials: J
authors.lastname: Farber
authors.affiliation: Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, United States.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Xin
authors.affiliation: Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, United States.
authors.forename: Ahmed Tafsirul
authors.initials: AT
authors.lastname: Hussain
authors.affiliation: Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, United States.
authors.forename: Kajol
authors.initials: K
authors.lastname: Shah
authors.affiliation: Department of Biological Sciences, Ohio University, Athens, OH 45701, United States.
authors.forename: Soichi
authors.initials: S
authors.lastname: Tanda
authors.affiliation: Department of Biomedical Sciences, Ohio University, Athens, OH 45701, United States.
authors.forename: Mark
authors.initials: M
authors.lastname: Berryman
authors.affiliation: Division of Nephrology, St. Louis University, St. Louis, MO 63110, United States.
authors.forename: John C
authors.initials: JC
authors.lastname: Edwards
authors.affiliation: Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, United States. Electronic address: Harpreet.singh@drexelmed.edu.
authors.forename: Harpreet
authors.initials: H
authors.lastname: Singh
mesh_terms: D000818:Animals; D018118:Chloride Channels / Q000032:analysis*; D002712:Chlorides / Q000378:metabolism*; D004330:Drosophila; D008809:Mice, Inbred C3H; D008929:Mitochondria, Heart / Q000201:enzymology* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C546620:CLIC1 protein, rat; C000612424:CLIC5 protein, rat; D018118:Chloride Channels; D002712:Chlorides; C467578:Clic4 protein, rat; D017382:Reactive Oxygen Species
keywords: Cardiomyocytes; Chloride intracellular channels; Intracellular ion channels; Mitochondria; Reactive oxygen species