Book chapter
Mitochondrial-Targeted Catalase: Extended Longevity and the Roles in Various Disease Models
Molecular Biology of Aging, Vol.146, pp.203-241
Progress in molecular biology and translational science, 146
2017
DOI: 10.1016/bs.pmbts.2016.12.015
PMID: 28253986
Abstract
The free-radical theory of aging was proposed more than 50 years ago. As one of the most popular mechanisms explaining the aging process, it has been extensively studied in several model organisms. However, the results remain controversial. The mitochondrial version of free-radical theory of aging proposes that mitochondria are both the primary sources of reactive oxygen species (ROS) and the primary targets of ROS-induced damage. One critical ROS is hydrogen peroxide, which is naturally degraded by catalase in peroxisomes or glutathione peroxidase within mitochondria. Our laboratory developed mice-overexpressing catalase targeted to mitochondria (mCAT), peroxisomes (pCAT), or the nucleus (nCAT) in order to investigate the role of hydrogen peroxide in different subcellular compartments in aging and age-related diseases. The mCAT mice have demonstrated the largest effects on life span and healthspan extension. This chapter will discuss the mCAT phenotype and review studies using mCAT to investigate the roles of mitochondrial oxidative stresses in various disease models, including metabolic syndrome and atherosclerosis, cardiac aging, heart failure, skeletal muscle pathology, sensory defect, neurodegenerative diseases, and cancer. As ROS has been increasingly recognized as essential signaling molecules that may be beneficial in hormesis, stress response and immunity, the potential pleiotropic, or adverse effects of mCAT are also discussed. Finally, the development of small-molecule mitochondrial-targeted therapeutic approaches is reviewed.
Details
- Title: Subtitle
- Mitochondrial-Targeted Catalase: Extended Longevity and the Roles in Various Disease Models
- Creators
- D-F Dai - University of Washington, Seattle, WA, United StatesY-A Chiao - University of Washington, Seattle, WA, United StatesG M Martin - University of Washington, Seattle, WA, United StatesD J Marcinek - University of Washington, Seattle, WA, United StatesN Basisty - University of Washington, Seattle, WA, United StatesE K Quarles - University of Washington, Seattle, WA, United StatesP S Rabinovitch - University of Washington, Seattle, WA, United States. Electronic address: PeterR@medicine.washington.edu
- Resource Type
- Book chapter
- Publication Details
- Molecular Biology of Aging, Vol.146, pp.203-241
- Publisher
- Netherlands
- Series
- Progress in molecular biology and translational science; 146
- DOI
- 10.1016/bs.pmbts.2016.12.015
- PMID
- 28253986
- ISSN
- 1877-1173
- eISSN
- 1878-0814
- Grant note
- R01 CA210916 / NCI NIH HHS
- Language
- English
- Date published
- 2017
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Radiation Oncology
- Record Identifier
- 9984046934302771
Metrics
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