Targeting the mitochondria to augment myocardial protection.
The dynamic regulation of the structure, function and turnover of mitochondria is recognized as an immutable control node maintaining cellular integrity and homeostasis. The term 'mitohormesis' has recently been coined to describe the adaptive reprogramming of mitochondrial biology in response to low levels of metabolic substrate deprivation to augment subsequent mitochondrial and cellular tolerance to biological stress. Disruption of these regulatory programs gives rise to cardiovascular and neurodegenerative diseases, and augmentation or fine-tuning of these programs may ameliorate mitochondrial and global cellular stress tolerance. This is in part via the regulation of reactive oxygen species, calcium homeostasis, and in response to caloric restriction, the capacity to augment DNA repair. The objective of this manuscript is to briefly review these regulatory programs and to postulate novel therapeutic approaches with the primary goal of modulating mitochondria to enhance tolerance to cardiac ischemic stress.
Schwartz
Daniel R
DR
Translational Medicine Branch, NHLBI, National Institutes of Health, Bethesda, MD 20892-1454, United States.
Sack
Michael N
MN
D055372:AMP-Activated Protein Kinases; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D016503:Drug Delivery Systems; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D019194:Ischemic Preconditioning / Q000379:methods; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009573:Nitrites / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000494:pharmacology
D000975:Antioxidants; D009097:Multienzyme Complexes; D009573:Nitrites; D009943:Organophosphorus Compounds; D013267:Stilbenes; D014451:Ubiquinone; C429014:mitoquinone; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D000077185:Resveratrol