Affordable Access

deepdyve-link
Publisher Website

Mitochondrial protein 18 is a positive apoptotic regulator in cardiomyocytes under oxidative stress.

Authors
  • Aung, Lynn H H1
  • Li, Yu-Zhen2
  • Yu, Hua3
  • Chen, Xiatian4
  • Yu, Zhongjie4
  • Gao, Jinning4
  • Li, Peifeng1
  • 1 Center for Molecular Genetics, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China [email protected] [email protected] , (China)
  • 2 Department of Pathophysiology, Institute of Basic Medical Science, PLA General Hospital, Beijing 100853, China. , (China)
  • 3 The Affiliated Cardiovascular Hospital of Qingdao University, Qingdao 266000, China. , (China)
  • 4 Center for Molecular Genetics, Institute for Translational Medicine, College of Medicine, Qingdao University, Qingdao 266021, China. , (China)
Type
Published Article
Journal
Clinical Science
Publisher
Portland Press
Publication Date
May 15, 2019
Volume
133
Issue
9
Pages
1067–1084
Identifiers
DOI: 10.1042/CS20190125
PMID: 31015359
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Accumulation of reactive oxygen species is a common phenomenon in cardiac stress conditions, for instance, coronary artery disease, aging-related cardiovascular abnormalities, and exposure to cardiac stressors such as hydrogen peroxide (H2O2). Mitochondrial protein 18 (Mtp18) is a novel mitochondrial inner membrane protein, shown to involve in the regulation of mitochondrial dynamics. Although Mtp18 is abundant in cardiac muscles, its role in cardiac apoptosis remains elusive. The present study aimed to detect the role of Mtp18 in H2O2-induced mitochondrial fission and apoptosis in cardiomyocytes. We studied the effect of Mtp18 in cardiomyocytes by modulating its expression with lentiviral construct of Mtp18-shRNA and Mtp18 c-DNA, respectively. We then analyzed mitochondrial morphological dynamics with MitoTracker Red staining; apoptosis with terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) and cell death detection assays; and protein expression with immunoblotting. Here, we observed that Mtp18 could regulate oxidative stress- mediated mitochondrial fission and apoptosis in cardiac myocytes. Mechanistically, we found that Mtp8 induced mitochondrial fission and apoptosis by enhancing dynamin-related protein 1 (Drp1) accumulation. Conversely, knockdown of Mtp18 interfered with Drp1-associated mitochondrial fission and subsequent activation of apoptosis in both HL-1 cells and primary cardiomyocytes. However, overexpression of Mtp18 alone was not sufficient to execute apoptosis when Drp1 was minimally expressed, suggesting that Mtp18 and Drp1 are interdependent in apoptotic cascade. Together, these data highlight the role of Mtp18 in cardiac apoptosis and provide a novel therapeutic insight to minimize cardiomyocyte loss via targetting mitochondrial dynamics. © 2019 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Report this publication

Statistics

Seen <100 times