Molecular identity of cardiac mitochondrial chloride intracellular channel proteins

Mitochondrion. 2016 Mar:27:6-14. doi: 10.1016/j.mito.2016.01.001. Epub 2016 Jan 9.

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.

Keywords: Cardiomyocytes; Chloride intracellular channels; Intracellular ion channels; Mitochondria; Reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chloride Channels / analysis*
  • Chlorides / metabolism*
  • Drosophila
  • Mice, Inbred C3H
  • Mitochondria, Heart / enzymology*
  • Mitochondria, Heart / metabolism
  • Myocytes, Cardiac / metabolism*
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism

Substances

  • CLIC1 protein, rat
  • CLIC5 protein, rat
  • Chloride Channels
  • Chlorides
  • Clic4 protein, rat
  • Reactive Oxygen Species