Reference - Detail
| RRC ID | 76330 |
|---|---|
| Author | Wu X, Nagasawa S, Muto K, Ueda M, Suzuki C, Abe T, Higashitani A. |
| Title | Mitochonic Acid 5 Improves Duchenne Muscular Dystrophy and Parkinson's Disease Model of Caenorhabditis elegans. |
| Journal | Int J Mol Sci |
| Abstract |
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. |
| Volume | 23(17) |
| Published | 2022-8-24 |
| DOI | 10.3390/ijms23179572 |
| PII | ijms23179572 |
| PMID | 36076995 |
| PMC | PMC9455831 |
| MeSH | Adenosine Triphosphate Animals Caenorhabditis elegans / genetics Humans Indoleacetic Acids Mammals Muscular Dystrophy, Duchenne* / drug therapy Muscular Dystrophy, Duchenne* / genetics Parkinson Disease* / drug therapy Phenylbutyrates Rotenone / pharmacology |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 13 |
| Altmetric score changes over past 6months | 0.0 |
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| C.elegans | tm1730 |