Dynamics of mitochondrial DNA nucleoids regulated by mitochondrial fission is essential for maintenance of homogeneously active mitochondria during neonatal heart development

Takaya Ishihara, Reiko Ban-Ishihara, Maki Maeda, Yui Matsunaga, Ayaka Ichimura, Sachiko Kyogoku, Hiroki Aoki, Shun Katada, Kazuto Nakada, Masatoshi Nomura, Noboru Mizushima, Katsuyoshi Mihara, Naotada Ishihara

研究成果: Contribution to journalArticle査読

92 被引用数 (Scopus)

抄録

Mitochondria are dynamic organelles, and their fusion and fission regulate cellular signaling, development, and mitochondrial homeostasis, including mitochondrial DNA (mtDNA) distribution. Cardiac myocytes have a specialized cytoplasmic structure where large mitochondria are aligned into tightly packed myofibril bundles; however, recent studies have revealed that mitochondrial dynamics also plays an important role in the formation and maintenance of cardiomyocytes. Here, we precisely analyzed the role of mitochondrial fission in vivo. The mitochondrial fission GTPase, Drp1, is highly expressed in the developing neonatal heart, and muscle-specific Drp1 knockout (Drp1-KO) mice showed neonatal lethality due to dilated cardiomyopathy. The Drp1 ablation in heart and primary cultured cardiomyocytes resulted in severe mtDNA nucleoid clustering and led to mosaic deficiency of mitochondrial respiration. The functional and structural alteration of mitochondria also led to immature myofibril assembly and defective cardiomyocyte hypertrophy. Thus, the dynamics of mtDNA nucleoids regulated by mitochondrial fission is required for neonatal cardiomyocyte development by promoting homogeneous distribution of active mitochondria throughout the cardiomyocytes.

本文言語英語
ページ(範囲)211-223
ページ数13
ジャーナルMolecular and cellular biology
35
1
DOI
出版ステータス出版済み - 2015

All Science Journal Classification (ASJC) codes

  • 分子生物学
  • 細胞生物学

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