Recombinant mitochondrial transcription factor A protein inhibits nuclear factor of activated T cells signaling and attenuates pathological hypertrophy of cardiac myocytes

• DOI: 10.1016/j.mito.2012.06.002
• Publication Date: 2012-06-18T05:18:58Z
• Authors: Takeo Fujino; Tomomi Ide; Masayoshi Yoshida; Ken Onitsuka; Atsushi Tanaka; Yuko Hata; Motohiro Nishida; Takako Takehara; Takaaki Kanemaru; Naoyuki Kitajima; Shinya Takazaki; Hitoshi Kurose; Dongchon Kang; Kenji Sunagawa
• Keywords: Male; 0303 health sciences; NFATC Transcription Factors; Hypertrophy; Recombinant Proteins; 3. Good health; DNA-Binding Proteins; Mitochondrial Proteins; Mice; 03 medical and health sciences; Animals; Humans; Myocytes, Cardiac; Cells, Cultured; Signal Transduction; Transcription Factors

The overexpression of mitochondrial transcription factor A (TFAM) attenuates the decrease in mtDNA copy number after myocardial infarction, ameliorates pathological hypertrophy, and markedly improves survival. However, non-transgenic strategy to increase mtDNA for the treatment of pathological hypertrophy remains unknown. We produced recombinant human TFAM protein (rhTFAM). rhTFAM rapidly entered into mitochondria of cultured cardiac myocytes. rhTFAM increased mtDNA and abolished the activation of nuclear factor of activated T cells (NFAT), which is well known to activate pathological hypertrophy. rhTFAM attenuated subsequent morphological hypertrophy of myocytes as well. rhTFAM would be an attractive molecule in attenuating cardiac pathological hypertrophy.