Mitochondrial content is preserved throughout disease progression in the mdx mouse model of Duchenne muscular dystrophy, regardless of taurine supplementation

Mitochondrial dysfunction is a pathological feature of Duchenne muscular dystrophy (DMD), a debilitating and fatal neuromuscular disorder characterized by progressive muscle wasting and weakness. Mitochondria are a source of cellular ATP involved in Ca regulation and apoptotic signaling. Amelioratin...

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Veröffentlicht in:American Journal of Physiology: Cell Physiology 2018-04, Vol.314 (4), p.C483-C491
Hauptverfasser: Barker, Robert G, Wyckelsma, Victoria L, Xu, Hongyang, Murphy, Robyn M
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container_issue 4
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container_title American Journal of Physiology: Cell Physiology
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creator Barker, Robert G
Wyckelsma, Victoria L
Xu, Hongyang
Murphy, Robyn M
description Mitochondrial dysfunction is a pathological feature of Duchenne muscular dystrophy (DMD), a debilitating and fatal neuromuscular disorder characterized by progressive muscle wasting and weakness. Mitochondria are a source of cellular ATP involved in Ca regulation and apoptotic signaling. Ameliorating aberrant mitochondrial function has therapeutic potential for reducing DMD disease severity. The dystrophic mdx mouse exhibits peak muscle damage at 21-28 days, which stabilizes after 8 wk. The amino acid taurine is implicated in mitochondrial health and function, with endogenous concentrations low when measured during the cycle of peak muscle damage in mdx mice. Using whole soleus and extensor digitorum longus (EDL) muscle homogenates from 28- and 70-day mdx mice, we found that there was no change in native state mitochondrial complexes using blue native-PAGE. NADH:ubiquinone oxidotreductase subunit-A9 (NDUFA9) protein abundance was lower in soleus muscle of 28- and 70-day mdx mice and EDL muscle of 70-day mdx mice compared with same muscles in WT (C57/BL10ScSn) animals. There were age-dependent increases in both NDUFA9 protein abundance and citrate synthase activity in soleus muscles of mdx and wild-type mice. There was no change in abundances of mitochondrial dynamics proteins mitofusin 2 (Mfn2) and mitochondrial dynamics protein 49 (MiD49). Taurine administration essentially did not affect any measurements of mitochondria. Collectively, these findings suggest mitochondrial content and dynamics are not reduced in the mdx mouse regardless of disease severity. We also elucidate that taurine affords no significant benefit to mitochondrial content or dynamics in the mdx mouse at either 28 or 70 days.
doi_str_mv 10.1152/ajpcell.00046.2017
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subjects Animals
Citrate (si)-Synthase - metabolism
Dietary Supplements
Disease Models, Animal
Disease Progression
Electron Transport Complex I - metabolism
Electron Transport Complex IV - metabolism
GTP Phosphohydrolases - metabolism
Male
Membrane Proteins - metabolism
Mice, Inbred C57BL
Mice, Inbred mdx
Mitochondria, Muscle - drug effects
Mitochondria, Muscle - metabolism
Mitochondria, Muscle - pathology
Mitochondrial Dynamics - drug effects
Mitochondrial Proteins - metabolism
Muscle, Skeletal - drug effects
Muscle, Skeletal - metabolism
Muscle, Skeletal - pathology
Muscular Dystrophy, Duchenne - drug therapy
Muscular Dystrophy, Duchenne - genetics
Muscular Dystrophy, Duchenne - metabolism
Muscular Dystrophy, Duchenne - pathology
Taurine - pharmacology
Time Factors
title Mitochondrial content is preserved throughout disease progression in the mdx mouse model of Duchenne muscular dystrophy, regardless of taurine supplementation
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