Open AccessA novel mutation in human EMD gene and mitochondrial dysfunction in emerin knockdown cardiomyocytes
Author(s) -
Du Zunhui,
Zhu Tinfang,
Lin Menglu,
Bao Yangyang,
Qiao Jing,
Lv Gang,
Xie Yinyin,
Li Qihen,
Quan Jinwei,
Xu Cathy,
Xie Yuan,
Wang Lingjie,
Yang Wenjie,
Wang Shengyue,
Wu Liqun,
Yin Tong,
Xie Yucai
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17532
Subject(s) - emerin , biology , lamin , gene knockdown , mitochondrion , downregulation and upregulation , microbiology and biotechnology , mutation , mfn2 , nonsense mutation , genetics , inner membrane , mitochondrial fusion , mitochondrial dna , gene , missense mutation , nuclear protein , transcription factor
Abstract Emerin is an inner nuclear envelope protein encoded by the EMD gene, mutations in which cause Emery–Dreifuss muscular dystrophy type 1 (EDMD1). Cardiac involvement has become a major threat to patients with EDMD1; however, the cardiovascular phenotype spectrums of emerinopathy and the mechanisms by which emerin regulates cardiac pathophysiology remain unclear. Here, we identified a novel nonsense mutation (c.C57G, p.Y19X) in the EMD gene in a Han Chinese family through high‐throughput sequencing. Two family members were found to have EDMD1 with muscle weakness and cardiac arrhythmia. Mechanistically, we first discovered that knockdown of emerin in HL‐1 or H9C2 cardiomyocytes lead to impaired mitochondrial oxidative phosphorylation capacity with downregulation of electron transport chain complex I and IV and upregulation of complex III and V. Moreover, loss of emerin in HL‐1 cells resulted in collapsed mitochondrial membrane potential, altered mitochondrial networks and downregulated multiple factors in RNA and protein level, such as PGC1α, DRP1, MFF, MFN2, which are involved in regulation of mitochondrial biogenesis, fission and fusion. Our findings suggest that targeting mitochondrial bioenergetics might be an effective strategy against cardiac disorders caused by EMD mutations.