Targeting the mitochondria to augment myocardial protection
- PMID: 18243790
- PMCID: PMC2361131
- DOI: 10.1016/j.coph.2007.12.008
Targeting the mitochondria to augment myocardial protection
Abstract
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.
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References
-
- Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, Ristow M. Glucose restriction extend Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab. 2007;6:280–293. [of outstanding interestThis original manuscript introduces the novel concept of mitohormesis and the role of caloric restriction in adaptation of the mitochondria.] - PubMed
-
- Johnson DT, Harris RA, French S, Blair PV, You J, Bemis K, Wang M, Balaban RS. The Tissue Heterogeneity of the Mammalian Mitochondrial Proteome. Am J Physiol Cell Physiol. 2006 [of outstanding interestThis original manuscript employs proteomics to demonstrate that mitochondrial proteins are distinctly regulated in different tissue types to reflect underlying functional preferences.] - PubMed
-
- McLeod CJ, Pagel I, Sack MN. The mitochondrial biogenesis regulatory program in cardiac adaptation to ischemia-a putative target for therapeutic intervention. Trends Cardiovasc Med. 2005;15:118–123. - PubMed
-
- Finck BN, Kelly DP. Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) regulatory cascade in cardiac physiology and disease. Circulation. 2007;115:2540–2548. - PubMed
-
- Arany Z, He H, Lin J, Hoyer K, Handschin C, Toka O, Ahmad F, Matsui T, Chin S, Wu PH, et al. Transcriptional coactivator PGC-1 alpha controls the energy state and contractile function of cardiac muscle. Cell Metab. 2005;1:259–271. - PubMed
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