Peroxisomal regulation of redox homeostasis and adipocyte metabolism

Abstract

Peroxisomes are ubiquitous cellular organelles required for specific pathways of fatty acid oxidation and lipid synthesis, and until recently their functions in adipocytes have not been well appreciated. Importantly, peroxisomes host many oxygen-consumption reactions and play a major role in generation and detoxification of reactive oxygen species (ROS) and reactive nitrogen species (RNS), influencing whole cell redox status. Here, we review recent progress in peroxisomal functions in lipid metabolism as related to ROS/RNS metabolism and discuss the roles of peroxisomal redox homeostasis in adipogenesis and adipocyte metabolism. We provide a framework for understanding redox regulation of peroxisomal functions in adipocytes together with testable hypotheses for developing therapies for obesity and the related metabolic diseases.

Keywords: Adipocytes; Lipid metabolism; Mitochondria; Peroxisomes; Redox.

Graphical abstract

Fig. 1

Metabolic pathways in peroxisomes and redox regulation. Enzymes in red are known to generate ROS or act as antioxidants. Metabolites in blue act as non-enzymatic antioxidants. Refer to the text for details. ACOX, acyl-CoA oxidase; Alkyl-G3P, 1-O-alkyl glycerol-3-phosphate; DBP, D-bifunctional protein; DHAP, dihydroxy acetone phosphate; HAOX, l-hydroxy acid oxidase; HACL1, 2-hydroxyacyl-CoA lyase 1; LBP, L-bifunctional protein; 2-OHFA, 2-hydroxy fatty acid; PHYH, phytanoyl-CoA 2-hydroxylase; PUFA, poly unsaturated fatty acid; VLCFA, very long chain fatty acid.

Fig. 2

Peroxisomal ROS scavenge system. Red characters denote ROS/RNS and macromolecular damaged by ROS. Blue characters denote nonenzymatic antioxidants. Refer to the text for details. GPX, glutathione peroxidase; GR, glutathione reductase; GSH, reduced glutathione; GSSG, oxidized glutathione; H₂O₂, hydrogen peroxide; iNOS, inducible nitric oxide synthase; L^•, lipid radical; LOO^•, lipid peroxyl radical; LOOH, lipid peroxide; LOH, lipid alcohol; LONP2, Lon protease 2; ^•NO, nitric oxide radical; O₂^•-, superoxide radical; OH^•, hydroxyl radical; ONOO⁻, peroxynitrite; PRDX, peroxiredoxin; PUFA, polyunsaturated fatty acid; SOD, superoxide mutase.