Astin 2013 Sci Rep
|Astin R, Bentham R, Djafarzadeh S, Horscroft JA, Kuc RE, Leung PS, Skipworth JR, Vicencio JM, Davenport AP, Murray AJ, Takala J, Jakob SM, Montgomery H, Szabadkai G (2013) No evidence for a local renin-angiotensin system in liver mitochondria. Sci Rep 3:2467.|
Abstract: 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.
Labels: MiParea: Respiration
Organism: Rat Tissue;cell: Liver Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS Pathway: N, S, CIV HRR: Oxygraph-2k
An Oroboros Oxygraph-2k, Innsbruck, Austria was used in this publication, whereas the "Graz, Austria" reference usually credits the Anton Paar/Oroboros Oxygraph, the first-generation instrument for high-resolution respirometry, which was replaced by the Oxygraph-2k in 2002.
- Further details: Gnaiger 2012 Abstract Bioblast-Gentle Science