西亚试剂：Identification and characterization of a functional mitocho

Identification and characterization of a functional mitochondrial angiotensin system

Abadir, Peter M.; Foster, D. 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.

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 activatesurface membrane Ang receptors. Alternatively, an intracellular renin-Ang system has been proposed, with a primary focus onnuclear Ang receptors. A mitochondrial Ang system has not been previously described. Here we report that functional Ang IItype 2 receptors are present on mitochondrial inner membranes and are colocalized with endogenous Ang. We demonstrate thatactivation 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 mitochondrialAng II type 1 receptor and decreased type 2 receptor density that is reversed by chronic treatment with the Ang II type 1receptor blocker losartan. The presence of a functional Ang system in human mitochondria provides a foundation for understandingthe interaction between mitochondria and chronic disease states and reveals potential therapeutic targets for optimizing mitochondrialfunction and decreasing chronic disease burden with aging.