Prenatal hormone stress triggers embryonic cardiac hypertrophy outcome by ubiquitin-dependent degradation of mitochondrial mitofusin 2

  • iScience. 2023 Dec 8;27(1):108690. doi: 10.1016/j.isci.2023.108690.
Chang-Yu Yan  1 ,  Yue Ye  1 ,  Han-Lu Mu  1 ,  Tong Wu  1 ,  Wen-Shan Huang  1 ,  Yan-Ping Wu  1 ,  Wan-Yang Sun  1 ,  Lei Liang  1 ,  Wen-Jun Duan  1 ,  Shu-Hua Ouyang  1 ,  Rui-Ting Huang  2 ,  Rong Wang  3 ,  Xin-Xin Sun  4 ,  Hiroshi Kurihara  1 ,  Yi-Fang Li  1 ,  Rong-Rong He  1  2  3
Affiliations
  • 1. Guangdong Engineering Research Center of Chinese Medicine & Disease Susceptibility, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, China.
  • 2. State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau 999078, China.
  • 3. School of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicinal Utilization, Yunnan University of Chinese Medicine, Kunming 650500, China.
  • 4. Jiujiang Maternal and Child Health Hospital, Jiujiang 332000, China.
PMID: 38235340 DOI: 10.1016/j.isci.2023.108690
Abstract

Prenatal stress has been extensively documented as a contributing factor to adverse cardiac development and function in fetuses and infants. The release of glucocorticoids (GCs), identified as a significant stressor, may be a potential factor inducing cardiac hypertrophy. However, the underlying mechanism remains largely unknown. Herein, we discovered that corticosterone (CORT) overload induced cardiac hypertrophy in embryonic chicks and fetal mice in vivo, as well as enlarged cardiomyocytes in vitro. The impaired mitochondria dynamics were observed in CORT-exposed cardiomyocytes, accompanied by dysfunction in Oxidative Phosphorylation and ATP production. This phenomenon was found to be linked to decreased mitochondrial fusion protein mitofusin 2 (MFN2). Subsequently, we found that CORT facilitated the ubiquitin-proteasome-system-dependent degradation of MFN2 with an enhanced binding of appoptosin to MFN2, serving as the underlying cause. Collectively, our findings provide a comprehensive understanding of the mechanisms by which exposure to stress Hormones induces cardiac hypertrophy in fetuses.

Keywords
Cardiovascular medicine; Molecular biology.
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