دورية أكاديمية
Mitochonic Acid 5 (MA-5) Facilitates ATP Synthase Oligomerization and Cell Survival in Various Mitochondrial Diseases
| العنوان: | Mitochonic Acid 5 (MA-5) Facilitates ATP Synthase Oligomerization and Cell Survival in Various Mitochondrial Diseases |
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| المؤلفون: | Tetsuro Matsuhashi, Takeya Sato, Shin-ichiro Kanno, Takehiro Suzuki, Akihiro Matsuo, Yuki Oba, Motoi Kikusato, Emi Ogasawara, Tai Kudo, Kosuke Suzuki, Osamu Ohara, Hiroko Shimbo, Fumika Nanto, Hiroaki Yamaguchi, Daisuke Saigusa, Yasuno Mukaiyama, Akiko Watabe, Koichi Kikuchi, Hisato Shima, Eikan Mishima, Yasutoshi Akiyama, Yoshitsugu Oikawa, HO Hsin-Jung, Yukako Akiyama, Chitose Suzuki, Mitsugu Uematsu, Masaki Ogata, Naonori Kumagai, Masaaki Toyomizu, Atsushi Hozawa, Nariyasu Mano, Yuji Owada, Setsuya Aiba, Teruyuki Yanagisawa, Yoshihisa Tomioka, Shigeo Kure, Sadayoshi Ito, Kazuto Nakada, Ken-ichiro Hayashi, Hitoshi Osaka, Takaaki Abe |
| المصدر: | EBioMedicine, Vol 20, Iss C, Pp 27-38 (2017) |
| بيانات النشر: | Elsevier, 2017. |
| سنة النشر: | 2017 |
| المجموعة: | LCC:Medicine LCC:Medicine (General) |
| مصطلحات موضوعية: | MA-5, Mitochondrial disease, ATPase dimer formation, Supercomplex, GDF-15, Medicine, Medicine (General), R5-920 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2352-3964 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2352396417302141; https://doaj.org/toc/2352-3964 |
| DOI: | 10.1016/j.ebiom.2017.05.016 |
| URL الوصول: | https://doaj.org/article/a69fd02b6914423ab9feee99f60fd27a |
| رقم الأكسشن: | edsdoj.69fd02b6914423ab9feee99f60fd27a |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text via ClinicalKey 
Full Text Finder | تدمد: | 23523964 |
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| DOI: | 10.1016/j.ebiom.2017.05.016 |