Identification and characterization of a functional mitochondrial angiotensin system

Peter Abadir, Darren Brian Foster, Michael Crow, Carol A. Cooke, Jasma J. Rucker, Alka Jain, Barbara J. Smith, Tyesha N. Burks, Ronald D. Cohn, Neal S Fedarko, Robert M. Carey, Brian O'Rourke, Jeremy D Walston

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)14849-14854
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number36
DOIs
StatePublished - Sep 6 2011

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Angiotensins
Angiotensin Receptors
Angiotensin Type 1 Receptor
Renin-Angiotensin System
Mitochondria
Chronic Disease
Angiotensin Type 2 Receptor
Angiotensin II Type 1 Receptor Blockers
Losartan
Mitochondrial Membranes
Cytoplasmic and Nuclear Receptors
Angiotensin II
Nitric Oxide
Respiration
Membranes
Therapeutics

Keywords

  • ATP
  • Bioenergetics
  • Frailty

ASJC Scopus subject areas

  • General

Cite this

Identification and characterization of a functional mitochondrial angiotensin system. / Abadir, Peter; Foster, Darren Brian; Crow, Michael; Cooke, Carol A.; Rucker, Jasma J.; Jain, Alka; Smith, Barbara J.; Burks, Tyesha N.; Cohn, Ronald D.; Fedarko, Neal S; Carey, Robert M.; O'Rourke, Brian; Walston, Jeremy D.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 36, 06.09.2011, p. 14849-14854.

Research output: Contribution to journalArticle

Abadir, Peter ; Foster, Darren Brian ; Crow, Michael ; Cooke, Carol A. ; Rucker, Jasma J. ; Jain, Alka ; Smith, Barbara J. ; Burks, Tyesha N. ; Cohn, Ronald D. ; Fedarko, Neal S ; Carey, Robert M. ; O'Rourke, Brian ; Walston, Jeremy D. / Identification and characterization of a functional mitochondrial angiotensin system. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 36. pp. 14849-14854.
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