Mitochonic Acid 5 (MA-5), a Derivative of the Plant Hormone Indole-3-Acetic Acid, Improves Survival of Fibroblasts from Patients with Mitochondrial Diseases

• DOI: 10.1620/tjem.236.225
• Publication Date: 2015-06-25T20:25:06Z
• Authors: Takehiro Suzuki; Hiroaki Yamaguchi; Motoi Kikusato; Tetsuro Matsuhashi; Akihiro Matsuo; Takeya Sato; Yuki Oba; Shun Watanabe; Daichi Minaki; Daisuke Saigusa; Hiroko Shimbo; Nobuyoshi Mori; Eikan Mishima; Hisato Shima; Yasutoshi Akiyama; Yoichi Takeuchi; Akinori Yuri; Koichi Kikuchi; Takafumi Toyohara; Chitose Suzuki; Masahiro Kohzuki; Jun-ichi Anzai; Nariyasu Mano; Shigeo Kure; Teruyuki Yanagisawa; Yoshihisa Tomioka; Masaaki Toyomizu; Sadayoshi Ito; Hitoshi Osaka; Ken-ichiro Hayashi; Takaaki Abe
• Keywords: Indole-3-acetic acid; Derivative (finance); Plant hormone

Mitochondria are key organelles implicated in a variety of processes related to energy and free radical generation, the regulation apoptosis, various signaling pathways. Mitochondrial dysfunction increases cellular oxidative stress depletes ATP inherited mitochondrial diseases also many other metabolic neurodegenerative diseases. characterized by respiratory chain, caused mutations genes encoded either nuclear DNA or DNA. We have hypothesized that chemicals increase levels may ameliorate seen To search for potential drugs diseases, we screened an in-house chemical library indole-3-acetic-acid analogs measuring Hep3B human hepatocellular carcinoma cells. thus identified mitochonic acid 5 (MA-5), 4-(2,4-difluorophenyl)-2-(1H-indol-3-yl)-4-oxobutanoic acid, as drug enhancing production. MA-5 is newly synthesized derivative plant hormone, indole-3-acetic acid. Importantly, improved survival fibroblasts established from patients with under stress-induced condition, including Leigh syndrome, MELAS (myopathy encephalopathy lactic acidosis stroke-like episodes), Leber's hereditary optic neuropathy, Kearns-Sayre syndrome. The was associated increased levels. Moreover, disease even inhibition phosphorylation electron transport chain. These data suggest could be therapeutic exerts its effect manner different anti-oxidant therapy.