No evidence for a local renin-angiotensin system in liver mitochondria

• Published in: Scientific reports Vol. 3; no. 1; p. 2467
• Main Authors: Astin, Ronan, Bentham, Robert, Djafarzadeh, Siamak, Horscroft, James A., Kuc, Rhoda E., Leung, Po Sing, Skipworth, James R. A., Vicencio, Jose M., Davenport, Anthony P., Murray, Andrew J., Takala, Jukka, Jakob, Stephan M., Montgomery, Hugh, Szabadkai, Gyorgy
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.08.2013; Nature Publishing Group
• Subjects: 631/45; 631/80/642/333/1465; 631/80/86/2363; 692/308; Angiotensin; Angiotensin II; Angiotensin II - pharmacokinetics; Angiotensin II - pharmacology; Animals; Binding sites; Cells, Cultured; Energy metabolism; Homeostasis; Humanities and Social Sciences; Liver; Metabolism; Mitochondria; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; multidisciplinary; Rats; Receptor, Angiotensin, Type 1 - metabolism; Renin; Renin-Angiotensin System - drug effects; Renin-Angiotensin System - physiology; Rodents; Science
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep02467

The circulating, endocrine renin-angiotensin system (RAS) is important to circulatory homeostasis, while ubiquitous tissue and cellular RAS play diverse roles, including metabolic regulation. Indeed, inhibition of RAS is associated with improved cellular oxidative capacity. Recently it has been suggested that an intra-mitochondrial RAS directly impacts on metabolism. Here we sought to rigorously explore this hypothesis. Radiolabelled ligand-binding and unbiased proteomic approaches were applied to purified mitochondrial sub-fractions from rat liver and the impact of AngII on mitochondrial function assessed. Whilst high-affinity AngII binding sites were found in the mitochondria-associated membrane (MAM) fraction, no RAS components could be detected in purified mitochondria. Moreover, AngII had no effect on the function of isolated mitochondria at physiologically relevant concentrations. We thus found no evidence of endogenous mitochondrial AngII production and conclude that the effects of AngII on cellular energy metabolism are not mediated through its direct binding to mitochondrial targets.