Cisd2 is Essential to Delaying Cardiac Aging and to Maintaining Heart Functions

Overview

Journal PLoS Biol

Specialty Biology

Date 2019 Oct 9

PMID 31593566

Citations 26

Authors

Chi-Hsiao Yeh

Zhao-Qing Shen

Shao-Yu Hsiung

Pei-Chun Wu

Yuan-Chi Teng

Yi-Ju Chou

Su-Wen Fang

Chian-Feng Chen

Yu-Ting Yan

Lung-Sen Kao

Cheng-Heng Kao

Ting-Fen Tsai

Affiliations

Soon will be listed here.

Abstract

CDGSH iron-sulfur domain-containing protein 2 (Cisd2) is pivotal to mitochondrial integrity and intracellular Ca2+ homeostasis. In the heart of Cisd2 knockout mice, Cisd2 deficiency causes intercalated disc defects and leads to degeneration of the mitochondria and sarcomeres, thereby impairing its electromechanical functioning. Furthermore, Cisd2 deficiency disrupts Ca2+ homeostasis via dysregulation of sarco/endoplasmic reticulum Ca2+-ATPase (Serca2a) activity, resulting in an increased level of basal cytosolic Ca2+ and mitochondrial Ca2+ overload in cardiomyocytes. Most strikingly, in Cisd2 transgenic mice, a persistently high level of Cisd2 is sufficient to delay cardiac aging and attenuate age-related structural defects and functional decline. In addition, it results in a younger cardiac transcriptome pattern during old age. Our findings indicate that Cisd2 plays an essential role in cardiac aging and in the heart's electromechanical functioning. They highlight Cisd2 as a novel drug target when developing therapies to delay cardiac aging and ameliorate age-related cardiac dysfunction.

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