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Reduced electron transport chain complex I protein abundance and function in Mfn2‐deficient myogenic progenitors lead to oxidative stress and mitochondria swelling
Author(s) -
Luo Nanjian,
Yue Feng,
Jia Zhihao,
Chen Jingjuan,
Deng Qing,
Zhao Yongju,
Kuang Shihuan
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202002464r
Subject(s) - mfn2 , mitochondrion , microbiology and biotechnology , myogenesis , myocyte , biology , mitochondrial fusion , skeletal muscle , respiratory chain , progenitor cell , chemistry , biochemistry , mitochondrial dna , stem cell , anatomy , gene
Mitochondrial remodeling through fusion and fission is crucial for progenitor cell differentiation but its role in myogenesis is poorly understood. Here, we characterized the function of mitofusin 2 (Mfn2), a mitochondrial outer membrane protein critical for mitochondrial fusion, in muscle progenitor cells (myoblasts). Mfn2 expression is upregulated during myoblast differentiation in vitro and muscle regeneration in vivo. Targeted deletion of Mfn2 gene in myoblasts ( Mfn2 MKO ) increases oxygen‐consumption rates (OCR) associated with the maximal respiration and spare respiratory capacity, and increased levels of reactive oxygen species (ROS). Skeletal muscles of Mfn2 MKO mice exhibit robust mitochondrial swelling with normal mitochondrial DNA content. Additionally, mitochondria isolated from Mfn2 MKO muscles have reduced OCR at basal state and for complex I respiration, associated with decreased levels of complex I proteins NDUFB8 (NADH ubiquinone oxidoreductase subunit B8) and NDUFS3 (NADH ubiquinone oxidoreductase subunit S3). However, Mfn2 MKO has no obvious effects on myoblast differentiation, muscle development and function, and muscle regeneration. These results demonstrate a novel role of Mfn2 in regulating mitochondrial complex I protein abundance and respiratory functions in myogenic progenitors and myofibers.