Apobec2 deficiency causes mitochondrial defects and mitophagy in skeletal muscle

Yusuke Sato, Hideaki Ohtsubo, Naohiro Nihei, Takane Kaneko, Yoriko Sato, Shin Ichi Adachi, Shinji Kondo, Mako Nakamura, Wataru Mizunoya, Hiroshi Iida, Ryuichi Tatsumi, Cristina Rada, Fumiaki Yoshizawa

研究成果: ジャーナルへの寄稿記事

3 引用 (Scopus)

抄録

Apobec2 is a member of the activation-induced deaminase/apolipoprotein B mRNA editing enzyme catalytic polypeptide cytidine deaminase family expressed in differentiated skeletal and cardiac muscle. We previously reported that Apobec2 deficiency in mice leads to a shift in muscle fiber type, myopathy, and diminished muscle mass. However, the mechanisms ofmyopathy caused by Apobec2 deficiency and its physiologic functions are unclear. Here we show that, although Apobec2 localizes to the sarcomeric Z-lines in mouse tissue and cultured myotubes, the sarcomeric structure is not affected in Apobec2-deficient muscle. In contrast, electron microscopy reveals enlarged mitochondria and mitochondria engulfed by autophagic vacuoles, suggesting that Apobec2 deficiency causes mitochondrial defects leading to increased mitophagy in skeletal muscle. Indeed, Apobec2 deficiency results in increased reactive oxygen species generation and depolarized mitochondria, leading to mitophagy as a defensive response. Furthermore, the exercise capacity of Apobec2-/- mice is impaired, implying Apobec2 deficiency results in ongoing muscle dysfunction. The presence of rimmed vacuoles in myofibers from 10-mo-old mice suggests that the chronic muscle damage impairs normal autophagy. We conclude that Apobec2 deficiency causes mitochondrial defects that increase muscle mitophagy, leading to myopathy and atrophy. Our findings demonstrate that Apobec2 is required for mitochondrial homeostasis to maintain normal skeletal muscle function.

元の言語英語
ページ(範囲)1428-1439
ページ数12
ジャーナルFASEB Journal
32
発行部数3
DOI
出版物ステータス出版済み - 3 1 2018

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Mitochondrial Degradation
Muscle
Skeletal Muscle
Muscles
Defects
Mitochondria
Muscular Diseases
Vacuoles
Cytidine Deaminase
Skeletal Muscle Fibers
Autophagy
Atrophy
Reactive Oxygen Species
Myocardium
Electron Microscopy
Homeostasis
Apolipoproteins B
Electron microscopy

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

これを引用

Sato, Y., Ohtsubo, H., Nihei, N., Kaneko, T., Sato, Y., Adachi, S. I., ... Yoshizawa, F. (2018). Apobec2 deficiency causes mitochondrial defects and mitophagy in skeletal muscle. FASEB Journal, 32(3), 1428-1439. https://doi.org/10.1096/fj.201700493R

Apobec2 deficiency causes mitochondrial defects and mitophagy in skeletal muscle. / Sato, Yusuke; Ohtsubo, Hideaki; Nihei, Naohiro; Kaneko, Takane; Sato, Yoriko; Adachi, Shin Ichi; Kondo, Shinji; Nakamura, Mako; Mizunoya, Wataru; Iida, Hiroshi; Tatsumi, Ryuichi; Rada, Cristina; Yoshizawa, Fumiaki.

:: FASEB Journal, 巻 32, 番号 3, 01.03.2018, p. 1428-1439.

研究成果: ジャーナルへの寄稿記事

Sato, Y, Ohtsubo, H, Nihei, N, Kaneko, T, Sato, Y, Adachi, SI, Kondo, S, Nakamura, M, Mizunoya, W, Iida, H, Tatsumi, R, Rada, C & Yoshizawa, F 2018, 'Apobec2 deficiency causes mitochondrial defects and mitophagy in skeletal muscle', FASEB Journal, 巻. 32, 番号 3, pp. 1428-1439. https://doi.org/10.1096/fj.201700493R
Sato, Yusuke ; Ohtsubo, Hideaki ; Nihei, Naohiro ; Kaneko, Takane ; Sato, Yoriko ; Adachi, Shin Ichi ; Kondo, Shinji ; Nakamura, Mako ; Mizunoya, Wataru ; Iida, Hiroshi ; Tatsumi, Ryuichi ; Rada, Cristina ; Yoshizawa, Fumiaki. / Apobec2 deficiency causes mitochondrial defects and mitophagy in skeletal muscle. :: FASEB Journal. 2018 ; 巻 32, 番号 3. pp. 1428-1439.
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abstract = "Apobec2 is a member of the activation-induced deaminase/apolipoprotein B mRNA editing enzyme catalytic polypeptide cytidine deaminase family expressed in differentiated skeletal and cardiac muscle. We previously reported that Apobec2 deficiency in mice leads to a shift in muscle fiber type, myopathy, and diminished muscle mass. However, the mechanisms ofmyopathy caused by Apobec2 deficiency and its physiologic functions are unclear. Here we show that, although Apobec2 localizes to the sarcomeric Z-lines in mouse tissue and cultured myotubes, the sarcomeric structure is not affected in Apobec2-deficient muscle. In contrast, electron microscopy reveals enlarged mitochondria and mitochondria engulfed by autophagic vacuoles, suggesting that Apobec2 deficiency causes mitochondrial defects leading to increased mitophagy in skeletal muscle. Indeed, Apobec2 deficiency results in increased reactive oxygen species generation and depolarized mitochondria, leading to mitophagy as a defensive response. Furthermore, the exercise capacity of Apobec2-/- mice is impaired, implying Apobec2 deficiency results in ongoing muscle dysfunction. The presence of rimmed vacuoles in myofibers from 10-mo-old mice suggests that the chronic muscle damage impairs normal autophagy. We conclude that Apobec2 deficiency causes mitochondrial defects that increase muscle mitophagy, leading to myopathy and atrophy. Our findings demonstrate that Apobec2 is required for mitochondrial homeostasis to maintain normal skeletal muscle function.",
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AU - Adachi, Shin Ichi

AU - Kondo, Shinji

AU - Nakamura, Mako

AU - Mizunoya, Wataru

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