MicroRNA-494 regulates mitochondrial biogenesis in skeletal muscle through mitochondrial transcription factor A and Forkhead box j3

DOI Web Site PubMed 被引用文献11件
  • Hirotaka Yamamoto
    Division of Endocrinology and Metabolism, Department of Medicine, Shiga University of Medical Science, Otsu, Japan
  • Katsutaro Morino
    Division of Endocrinology and Metabolism, Department of Medicine, Shiga University of Medical Science, Otsu, Japan
  • Yoshihiko Nishio
    Division of Endocrinology and Metabolism, Department of Medicine, Shiga University of Medical Science, Otsu, Japan
  • Satoshi Ugi
    Division of Endocrinology and Metabolism, Department of Medicine, Shiga University of Medical Science, Otsu, Japan
  • Takeshi Yoshizaki
    Division of Endocrinology and Metabolism, Department of Medicine, Shiga University of Medical Science, Otsu, Japan
  • Atsunori Kashiwagi
    Division of Endocrinology and Metabolism, Department of Medicine, Shiga University of Medical Science, Otsu, Japan
  • Hiroshi Maegawa
    Division of Endocrinology and Metabolism, Department of Medicine, Shiga University of Medical Science, Otsu, Japan

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<jats:p> MicroRNAs (miRNAs) are important posttranscriptional regulators of various biological pathways. In this study, we focused on the role of miRNAs during mitochondrial biogenesis in skeletal muscle. The expression of miR-494 was markedly decreased in murine myoblast C<jats:sub>2</jats:sub>C<jats:sub>12</jats:sub> cells during myogenic differentiation, accompanied by an increase in mtDNA. Furthermore, the expression of predicted target genes for miR-494, including mitochondrial transcription factor A (mtTFA) and Forkhead box j3 (Foxj3), was posttranscriptionally increased during myogenic differentiation. Knockdown of miR-494 resulted in increased mitochondrial content and upregulation of mtTFA and Foxj3 at the protein level. A 3′-untranslated region reporter assay revealed that miR-494 knockdown directly upregulated the luciferase activity of mtTFA and Foxj3. All of these observations were reversed by overexpression of miR-494. Furthermore, the miR-494 content significantly decreased after endurance exercise in C57BL/6J mice, accompanied by an increase in expression of mtTFA and Foxj3 proteins. These results suggest that miR-494 regulates mitochondrial biogenesis by downregulating mtTFA and Foxj3 during myocyte differentiation and skeletal muscle adaptation to physical exercise. </jats:p>

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