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Identification and characterization of a functional mitochondrial angiotensin system.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2011 Sep 06; Vol. 108 (36), pp. 14849-54. Date of Electronic Publication: 2011 Aug 18. - Publication Year :
- 2011
-
Abstract
- The renin-angiotensin (Ang) system regulates multiple physiological functions through Ang II type 1 and type 2 receptors. Prior studies suggest an intracellular pool of Ang II that may be released in an autocrine manner upon stretch to activate surface membrane Ang receptors. Alternatively, an intracellular renin-Ang system has been proposed, with a primary focus on nuclear Ang receptors. A mitochondrial Ang system has not been previously described. Here we report that functional Ang II type 2 receptors are present on mitochondrial inner membranes and are colocalized with endogenous Ang. We demonstrate that activation of the mitochondrial Ang system is coupled to mitochondrial nitric oxide production and can modulate respiration. In addition, we present evidence of age-related changes in mitochondrial Ang receptor expression, i.e., increased mitochondrial Ang II type 1 receptor and decreased type 2 receptor density that is reversed by chronic treatment with the Ang II type 1 receptor blocker losartan. The presence of a functional Ang system in human mitochondria provides a foundation for understanding the interaction between mitochondria and chronic disease states and reveals potential therapeutic targets for optimizing mitochondrial function and decreasing chronic disease burden with aging.
- Subjects :
- Aging drug effects
Aging metabolism
Angiotensin II Type 1 Receptor Blockers pharmacology
Animals
Autocrine Communication drug effects
Autocrine Communication physiology
Cell Line
Chronic Disease
Humans
Losartan pharmacology
Mice
Nitric Oxide metabolism
Oxygen Consumption drug effects
Oxygen Consumption physiology
Renin-Angiotensin System drug effects
Kidney metabolism
Mitochondria metabolism
Mitochondrial Membranes metabolism
Receptor, Angiotensin, Type 1 metabolism
Receptor, Angiotensin, Type 2 metabolism
Renin-Angiotensin System physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 108
- Issue :
- 36
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 21852574
- Full Text :
- https://doi.org/10.1073/pnas.1101507108