title: Mitochondrial function and regulation of macrophage sterol metabolism and inflammatory responses.
abstract: The aim of this review is to explore the role of mitochondria in regulating macrophage sterol homeostasis and inflammatory responses within the aetiology of atherosclerosis. Macrophage generation of oxysterol activators of liver X receptors (LXRs), via sterol 27-hydroxylase, is regulated by the rate of flux of cholesterol to the inner mitochondrial membrane, via a complex of cholesterol trafficking proteins. Oxysterols are key signalling molecules, regulating the transcriptional activity of LXRs which coordinate macrophage sterol metabolism and cytokine production, key features influencing the impact of these cells within atherosclerotic lesions. The precise identity of the complex of proteins mediating mitochondrial cholesterol trafficking in macrophages remains a matter of debate, but may include steroidogenic acute regulatory protein and translocator protein. There is clear evidence that targeting either of these proteins enhances removal of cholesterol via LXRα-dependent induction of ATP binding cassette transporters (ABCA1, ABCG1) and limits the production of inflammatory cytokines; interventions which influence mitochondrial structure and bioenergetics also impact on removal of cholesterol from macrophages. Thus, molecules which can sustain or improve mitochondrial structure, the function of the electron transport chain, or increase the activity of components of the protein complex involved in cholesterol transfer, may therefore have utility in limiting or regressing atheroma development, reducing the incidence of coronary heart disease and myocardial infarction.
authors.affiliation: Annette Graham, Anne-Marie Allen, Department of Life Sciences, School of Health and Life Sciences and the Institute for Applied Health Research (Diabetes Research Group), Glasgow Caledonian University, G4 0BA Glasgow, United Kingdom.
authors.forename: Annette
authors.initials: A
authors.lastname: Graham
authors.affiliation: Annette Graham, Anne-Marie Allen, Department of Life Sciences, School of Health and Life Sciences and the Institute for Applied Health Research (Diabetes Research Group), Glasgow Caledonian University, G4 0BA Glasgow, United Kingdom.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Allen
keywords: ATP binding cassette transporters; Apolipoproteins; Atherosclerosis; Cholesterol; High density lipoproteins; Liver X receptors; Macrophage; Mitochondria (dys)function; Scavenger receptor B1; Sterol 27-hydroxylase