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DELE1 is protective for mitochondrial cardiomyopathy.

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.

SUBMITTER: Huynh H

PROVIDER: S-EPMC10387237 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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DELE1 is protective for mitochondrial cardiomyopathy.

Huynh Helen H Zhu Siting S Lee Sharon S Bao Yutong Y Pang Jing J Nguyen Anh A Gu Yusu Y Chen Chao C Ouyang Kunfu K Evans Sylvia M SM Fang Xi X

Journal of molecular and cellular cardiology 20221217

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 d ...[more]

PMID: 36539111

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Cytosolic retention of HtrA2 during mitochondrial protein import stress triggers the DELE1-HRI pathway.

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