Age-related alterations in oxidatively damaged proteins of mouse skeletal muscle mitochondrial electron transport
Kashyap B Choksi1, Jonathan E Nuss, James H Deford
1Department of Biochemistry & Molecular Biology, University of Texas Medical Branch, 301 University Blvd., Mail Route 0643, Galveston, TX 77555-0643, USA.
Abstract:
Age-associated mitochondrial dysfunction is a major source of reactive oxygen species (ROS) and oxidative modification to proteins. Mitochondrial electron transport chain (ETC) complexes I and III are the sites of ROS production and we hypothesize that proteins of the ETC complexes are primary targets of ROS-mediated modification which impairs their structure and function. The pectoralis, primarily an aerobic red muscle, and quadriceps, primarily an anaerobic white muscle, have different rates of respiration and oxygen-carrying capacity, and hence, different rates of ROS production. This raises the question of whether these muscles exhibit different levels of oxidative protein modification. Our studies reveal that the pectoralis shows a dramatic age-related decline in almost all complex activities that correlates with increased oxidative modification. Similar complex proteins were modified in the quadriceps, at a significantly lower level with less change in enzyme and ETC coupling function. We postulate that mitochondrial ROS causes damage to specific ETC subunits which increases with age and leads to further mitochondrial dysfunction. We conclude that physiological characteristics of the pectoralis vs quadriceps may play a role in age-associated rate of mitochondrial dysfunction and in the decline in tissue function.
Insights
Aging mitochondria produce reactive oxygen species (ROS), damaging proteins. Muscle type influences this oxidative damage, with aerobic pectoralis showing more age-related decline than anaerobic quadriceps.
Area of Science:
- Mitochondrial biology
- Aging research
- Muscle physiology
Background:
- Mitochondrial dysfunction and reactive oxygen species (ROS) production increase with age.
- Oxidative modification of proteins, particularly within the electron transport chain (ETC) complexes, is a key consequence.
- Specific muscle types may exhibit differential susceptibility to age-related oxidative stress.
Purpose of the Study:
- To investigate age-associated oxidative modification of mitochondrial ETC proteins in different muscle types.
- To compare the levels of oxidative damage and functional decline in aerobic (pectoralis) versus anaerobic (quadriceps) muscles.
- To determine if inherent physiological differences between muscle types influence the rate of mitochondrial dysfunction.
Main Methods:
- Comparative analysis of mitochondrial protein oxidation in pectoralis and quadriceps muscles from aged subjects.
- Assay of electron transport chain (ETC) complex activities and coupling function.
- Quantification of oxidative modifications on specific ETC protein subunits.
Main Results:
- The pectoralis muscle exhibited a significant age-related decrease in ETC complex activities, strongly correlating with increased oxidative protein modification.
- Similar ETC proteins were modified in the quadriceps muscle, but to a substantially lower extent.
- Quadriceps muscle showed less age-related decline in enzyme activity and ETC coupling function compared to pectoralis.
Conclusions:
- Age-associated mitochondrial ROS leads to specific ETC subunit damage, exacerbating mitochondrial dysfunction.
- Physiological characteristics, such as aerobic versus anaerobic metabolism, influence the rate of age-related mitochondrial dysfunction.
- Differences in pectoralis and quadriceps muscle physiology contribute to varying rates of age-associated mitochondrial dysfunction and tissue function decline.
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