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

Abstract

Mitochondria are key organelles implicated in a variety of processes related to energy and free radical generation, the regulation of apoptosis, and various signaling pathways. Mitochondrial dysfunction increases cellular oxidative stress and depletes ATP in a variety of inherited mitochondrial diseases and also in many other metabolic and neurodegenerative diseases. Mitochondrial diseases are characterized by the dysfunction of the mitochondrial respiratory chain, caused by mutations in the genes encoded by either nuclear DNA or mitochondrial DNA. We have hypothesized that chemicals that increase the cellular ATP levels may ameliorate the mitochondrial dysfunction seen in mitochondrial diseases. To search for the potential drugs for mitochondrial diseases, we screened an in-house chemical library of indole-3-acetic-acid analogs by measuring the cellular ATP levels in Hep3B human hepatocellular carcinoma cells. We have thus identified mitochonic acid 5 (MA-5), 4-(2,4-difluorophenyl)-2-(1H-indol-3-yl)-4-oxobutanoic acid, as a potential drug for enhancing ATP production. MA-5 is a newly synthesized derivative of the plant hormone, T. Suzuki et al. 226

Mitochonic Acid 5 Binds Mitochondria and Ameliorates Renal Tubular and Cardiac Myocyte Damage

“…Here, we report that a newly synthesized indole acetic acid (IAA) derivative, mitochonic acid 5 (MA-5), 5 targets the mitochondrial protein mitofilin and facilitates ATP production, protecting against AKI and renal respiration damage in Mitomice. Our finding changes the focus of the search for drugs for mitochondrial and mitochondrial-related renal diseases, such as AKI, CKD, and SRNS.…”

“…Recently, we have reported that MA-5 increased the cellular ATP level and the improved survival of fibroblasts from patients with mitochondrial diseases. 5 Thus, MA-5 might protect tubular cells from IRI by cisplatin by maintaining intracellular ATP levels.…”

A View of the Therapy for Bell’s Palsy Based on Molecular Biological Analyses of Facial Muscles

“…MA-5 targets the mitochondrial protein mitofilin at the crista junction of the inner membrane and can be a novel agent for treating diseases associated with mitochondrial dysfunction [5,6] . In patients with SD having Bell's palsy, mitochondrial cytopathy may develop with ATP synthesis impairment.…”

Comparison study of gut microbiota in case of Parkinson’s disease and other neurological disorders

“…Сама β-индолилуксусная кислота оказывает туморо-токсический ýффект из-за повреждения ДНК клеток [28,29]. Одно из производных β-индо-лилуксусной кислоты, митохониевая кислота, оказывает защитное воздействие на фибробла-сты, полученные от больных с нейродегенера-тивной патологией, вероятнее всего благодаря олигомеризации АТФ-синтазы и последующей продукции большего количества АТФ [30]. По-ражение митохондрий является одним из вероят-ных патогенетических механизмов, приводящих к развитию болезни Паркинсона.…”