DELE1 is protective for mitochondrial cardiomyopathy

Helen Huynh; Siting Zhu; Sharon Lee; Yutong Bao; Jing Pang; Anh Nguyen; Yusu Gu; Chao Chen; Kunfu Ouyang; Sylvia M Evans; Xi Fang

doi:10.1016/j.yjmcc.2022.12.003

DELE1 is protective for mitochondrial cardiomyopathy

J Mol Cell Cardiol. 2023 Feb:175:44-48. doi: 10.1016/j.yjmcc.2022.12.003. Epub 2022 Dec 17.

Authors

Helen Huynh¹, Siting Zhu², Sharon Lee¹, Yutong Bao¹, Jing Pang¹, Anh Nguyen¹, Yusu Gu¹, Chao Chen¹, Kunfu Ouyang³, Sylvia M Evans⁴, Xi Fang⁵

Affiliations

¹ Department of Medicine, University of California San Diego, La Jolla, CA, USA.
² Department of Medicine, University of California San Diego, La Jolla, CA, USA; Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, School of Chemical Biology and Biotechnology, State Key Laboratory of Chemical Oncogenomics, Peking University Shenzhen Graduate School, Shenzhen, China.
³ Department of Cardiovascular Surgery, Peking University Shenzhen Hospital, School of Chemical Biology and Biotechnology, State Key Laboratory of Chemical Oncogenomics, Peking University Shenzhen Graduate School, Shenzhen, China.
⁴ Department of Medicine, University of California San Diego, La Jolla, CA, USA; Department of Pharmacology, University of California San Diego, La Jolla, CA, USA; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
⁵ Department of Medicine, University of California San Diego, La Jolla, CA, USA. Electronic address: xifang@ucsd.edu.

Abstract

Mitochondrial dysfunction in heart triggers an integrated stress response (ISR) through phosphorylation of eIF2α and subsequent ATF4 activation. DAP3 Binding Cell Death Enhancer 1 (DELE1) is a mitochondrial protein recently found to be critical for mediating mitochondrial stress-triggered ISR (MSR)-induced eIF2α-ATF4 pathway activation. However, the specific role of DELE1 in heart at baseline or in response to mitochondrial stress remains largely unknown. In this study, we report that DELE1 is dispensable for cardiac development and function under baseline conditions. Conversely, DELE1 is essential for mediating an adaptive response to mitochondrial dysfunction-triggered stress in the heart, playing a protective role in mitochondrial cardiomyopathy.

Keywords: Dele1; Integrated stress response; Mitochondrial cardiomyopathy; Mitochondrial stress.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cardiomyopathies* / genetics
Cardiomyopathies* / metabolism
Humans
Mitochondria* / genetics
Mitochondria* / metabolism
Phosphorylation

Abstract

Publication types

MeSH terms

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