Mitochondrial ROS and mitochondria-targeted antioxidants in the aged heart

Bou-Teen D., Kaludercic N., Weissman D., Turan B., Maack C., Di Lisa F., ...More

FREE RADICAL BIOLOGY AND MEDICINE, vol.167, pp.109-124, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 167
  • Publication Date: 2021
  • Doi Number: 10.1016/j.freeradbiomed.2021.02.043
  • Journal Name: FREE RADICAL BIOLOGY AND MEDICINE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Page Numbers: pp.109-124
  • Keywords: Aging, Cardiomyocytes, Cardioprotection, Sarcoplasmic reticulum, AGEs, ISCHEMIA-REPERFUSION INJURY, OXYGEN SPECIES PRODUCTION, PERMEABILITY TRANSITION PORE, GLYCATION END-PRODUCTS, REDOX-OPTIMIZED ROS, LIFE-SPAN EXTENSION, OXIDATIVE STRESS, SKELETAL-MUSCLE, SUPEROXIDE-PRODUCTION, NADPH OXIDASE
  • Lokman Hekim University Affiliated: Yes

Abstract

Excessive mitochondrial ROS production has been causally linked to the pathophysiology of aging in the heart and other organs, and plays a deleterious role in several age-related cardiac pathologies, including myocardial ischemia-reperfusion injury and heart failure, the two worldwide leading causes of death and disability in the elderly. However, ROS generation is also a fundamental mitochondrial function that orchestrates several signaling pathways, some of them exerting cardioprotective effects. In cardiac myocytes, mitochondria are particularly abundant and are specialized in subcellular populations, in part determined by their relationships with other organelles and their cyclic calcium handling activity necessary for adequate myocardial contraction/ relaxation and redox balance. Depending on their subcellular location, mitochondria can themselves be differentially targeted by ROS and display distinct age-dependent functional decline. Thus, precise mitochondriatargeted therapies aimed at counteracting unregulated ROS production are expected to have therapeutic benefits in certain aging-related heart conditions. However, for an adequate design of such therapies, it is necessary to unravel the complex and dynamic interactions between mitochondria and other cellular processes.