@article{2dc02fbd1a4d48ed810c406aed5f7e16,
title = "Mitochonic Acid 5 (MA-5) Facilitates ATP Synthase Oligomerization and Cell Survival in Various Mitochondrial Diseases",
abstract = "Mitochondrial dysfunction increases oxidative stress and depletes ATP in a variety of disorders. Several antioxidant therapies and drugs affecting mitochondrial biogenesis are undergoing investigation, although not all of them have demonstrated favorable effects in the clinic. We recently reported a therapeutic mitochondrial drug mitochonic acid MA-5 (Tohoku J. Exp. Med., 2015). MA-5 increased ATP, rescued mitochondrial disease fibroblasts and prolonged the life span of the disease model “Mitomouse” (JASN, 2016). To investigate the potential of MA-5 on various mitochondrial diseases, we collected 25 cases of fibroblasts from various genetic mutations and cell protective effect of MA-5 and the ATP producing mechanism was examined. 24 out of the 25 patient fibroblasts (96%) were responded to MA-5. Under oxidative stress condition, the GDF-15 was increased and this increase was significantly abrogated by MA-5. The serum GDF-15 elevated in Mitomouse was likewise reduced by MA-5. MA-5 facilitates mitochondrial ATP production and reduces ROS independent of ETC by facilitating ATP synthase oligomerization and supercomplex formation with mitofilin/Mic60. MA-5 reduced mitochondria fragmentation, restores crista shape and dynamics. MA-5 has potential as a drug for the treatment of various mitochondrial diseases. The diagnostic use of GDF-15 will be also useful in a forthcoming MA-5 clinical trial.",
keywords = "ATPase dimer formation, GDF-15, MA-5, Mitochondrial disease, Supercomplex",
author = "Tetsuro Matsuhashi and Takeya Sato and Kanno, {Shin ichiro} and Takehiro Suzuki and Akihiro Matsuo and Yuki Oba and Motoi Kikusato and Emi Ogasawara and Tai Kudo and Kosuke Suzuki and Osamu Ohara and Hiroko Shimbo and Fumika Nanto and Hiroaki Yamaguchi and Daisuke Saigusa and Yasuno Mukaiyama and Akiko Watabe and Koichi Kikuchi and Hisato Shima and Eikan Mishima and Yasutoshi Akiyama and Yoshitsugu Oikawa and Hsin-Jung, {H. O.} and Yukako Akiyama and Chitose Suzuki and Mitsugu Uematsu and Masaki Ogata and Naonori Kumagai and Masaaki Toyomizu and Atsushi Hozawa and Nariyasu Mano and Yuji Owada and Setsuya Aiba and Teruyuki Yanagisawa and Yoshihisa Tomioka and Shigeo Kure and Sadayoshi Ito and Kazuto Nakada and Hayashi, {Ken ichiro} and Hitoshi Osaka and Takaaki Abe",
note = "Funding Information: This works was supported in part by National grant-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (26670070), Translational Research Network Program (B20) and research support from the Dainippon-Sumitomo Pharm. and Daiichi-Sankyo Pharm. T.H., F.N. and H.-J.H are hired by a collaborative research grant of DSP. Publisher Copyright: {\textcopyright} 2017 The Authors",
year = "2017",
month = jun,
doi = "10.1016/j.ebiom.2017.05.016",
language = "English",
volume = "20",
pages = "27--38",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier BV",
}