Mitochonic Acid 5 (MA-5) enhances mitochondrial ATP production, restores fibroblasts from mitochondrial disease patients and extends the lifespan of the disease model “Mitomouse”. Additionally, MA-5 interacts with mitofilin and modulates the mitochondrial inner membrane organizing system (MINOS) in mammalian cultured cells. Here, we used the nematode Caenorhabditis elegans to investigate whether MA-5 improves the Duchenne muscular dystrophy (DMD) model. Firstly, we confirmed the efficient penetration of MA-5 in the mitochondria of C. elegans. MA-5 also alleviated symptoms such as movement decline, muscular tone, mitochondrial fragmentation and Ca2+ accumulation of the DMD model. To assess the effect of MA-5 on mitochondria perturbation, we employed a low concentration of rotenone with or without MA-5. MA-5 significantly suppressed rotenone-induced mitochondria reactive oxygen species (ROS) increase, mitochondrial network fragmentation and nuclear destruction in body wall muscles as well as endogenous ATP levels decline. In addition, MA-5 suppressed rotenone-induced degeneration of dopaminergic cephalic (CEP) neurons seen in the Parkinson’s disease (PD) model. Furthermore, the application of MA-5 reduced mitochondrial swelling due to the immt-1 null mutation. These results indicate that MA-5 has broad mitochondrial homing and MINOS stabilizing activity in metazoans and may be a therapeutic agent for these by ameliorating mitochondrial dysfunction in DMD and PD.

The mitochondrial-homing drug MA-5 ameliorates the pathophysiology of human mitochondrial-disease fibroblasts and Caenorhabditis elegans DMD and PD disease models. Here, we found that MA-5 could suppress the age-related decline in motor performance, loss of muscle mitochondria, and degeneration of dopaminergic neurons associated with mitochondrial Ca2+ overload in C. elegans. These suggest that MA-5 may act as an anti-aging agent against a wide range of neuromuscular dysfunctions in metazoan.

Mitochonic acid-5 ameliorates the pathophysiology of human mitochondrial-disease fibroblasts and Caenorhabditis elegans Duchenne muscular dystrophy and Parkinson’s disease models. Here, we found that 10 μM MA-5 attenuates the age-related decline in motor performance, loss of muscle mitochondria, and degeneration of dopaminergic neurons associated with mitochondrial Ca2+ overload in C. elegans. These findings suggest that MA-5 may act as an anti-aging agent against a wide range of neuromuscular dysfunctions in metazoans.