Journal article
Type II skeletal myofibers possess unique properties that potentiate mitochondrial H2O2 generation
American Journal of Physiology: Cell Physiology, Vol.290(3), pp.C844-C851
03/2006
DOI: 10.1152/ajpcell.00402.2005
PMID: 16251473
Abstract
Mitochondrial dysfunction is implicated in a number of skeletal muscle pathologies, most notably aging-induced atrophy and loss of type II myofibers. Although oxygen-derived free radicals are thought to be a primary cause of mitochondrial dysfunction, the underlying factors governing mitochondrial superoxide production in different skeletal myofiber types is unknown. Using a novel in situ approach to measure H2O2 production (indicator of superoxide formation) in permeabilized rat skeletal muscle fiber bundles, we found that mitochondrial free radical leak (H2O2 produced/O2 consumed) is two- to threefold higher ( P < 0.05) in white (WG, primarily type IIB fibers) than in red (RG, type IIA) gastrocnemius or soleus (type I) myofibers during basal respiration supported by complex I (pyruvate + malate) or complex II (succinate) substrates. In the presence of respiratory inhibitors, maximal rates of superoxide produced at both complex I and complex III are markedly higher in RG and WG than in soleus muscle despite ∼50% less mitochondrial content in WG myofibers. Duplicate experiments conducted with ±exogenous superoxide dismutase revealed striking differences in the topology and/or dismutation of superoxide in WG vs. soleus and RG muscle. When normalized for mitochondrial content, overall H2O2 scavenging capacity is lower in RG and WG fibers, whereas glutathione peroxidase activity, which is largely responsible for H2O2 removal in mitochondria, is similar in all three muscle types. These findings suggest that type II myofibers, particularly type IIB, possess unique properties that potentiate mitochondrial superoxide production and/or release, providing a potential mechanism for the heterogeneous development of mitochondrial dysfunction in skeletal muscle.
Details
- Title: Subtitle
- Type II skeletal myofibers possess unique properties that potentiate mitochondrial H2O2 generation
- Creators
- Ethan J AndersonP. Darrell Neufer
- Resource Type
- Journal article
- Publication Details
- American Journal of Physiology: Cell Physiology, Vol.290(3), pp.C844-C851
- DOI
- 10.1152/ajpcell.00402.2005
- PMID
- 16251473
- ISSN
- 0363-6143
- eISSN
- 1522-1563
- Language
- English
- Date published
- 03/2006
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Fraternal Order of Eagles Diabetes Research Center; Health and Human Physiology
- Record Identifier
- 9984065313002771
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