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

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; Montgomery, Hugh; Szabadkai, Gyorgy (2013). No evidence for a local renin-angiotensin system in liver mitochondria. Scientific Reports, 3(1), p. 2467. Nature Publishing Group 10.1038/srep02467

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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.

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pavillon 52 > Forschungsgruppe Intensivmedizin
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)

UniBE Contributor:

Djafarzadeh, Siamak; Takala, Jukka and Jakob, Stephan

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2045-2322

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Alessandra Angelini

Date Deposited:

04 Jul 2014 07:55

Last Modified:

08 Sep 2017 10:26

Publisher DOI:

10.1038/srep02467

Uncontrolled Keywords:

Biochemistry, Energy metabolism, Hormone receptors, Medical research

BORIS DOI:

10.7892/boris.54237

URI:

https://boris.unibe.ch/id/eprint/54237

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