title: Models of plasma membrane organization can be applied to mitochondrial membranes to target human health and disease with polyunsaturated fatty acids.
abstract: Bioactive n-3 polyunsaturated fatty acids (PUFA), abundant in fish oil, have potential for treating symptoms associated with inflammatory and metabolic disorders; therefore, it is essential to determine their fundamental molecular mechanisms. Recently, several labs have demonstrated the n-3 PUFA docosahexaenoic acid (DHA) exerts anti-inflammatory effects by targeting the molecular organization of plasma membrane microdomains. Here we briefly review the evidence that DHA reorganizes the spatial distribution of microdomains in several model systems. We then emphasize how models on DHA and plasma membrane microdomains can be applied to mitochondrial membranes. We discuss the role of DHA acyl chains in regulating mitochondrial lipid-protein clustering, and how these changes alter several aspects of mitochondrial function. In particular, we summarize effects of DHA on mitochondrial respiration, electron leak, permeability transition, and mitochondrial calcium handling. Finally, we conclude by postulating future experiments that will augment our understanding of DHA-dependent membrane organization in health and disease.
authors.affiliation: Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina University, 600 Moye Blvd, Greenville, NC 28590, USA. shaikhsa@ecu.edu
authors.forename: Saame
authors.initials: S
authors.lastname: Raza Shaikh
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D020013:Calcium Signaling; D002308:Cardiolipins / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D004579:Electron Transport; D015525:Fatty Acids, Omega-3 / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism*; D008659:Metabolic Diseases / Q000178:diet therapy* / Q000276:immunology; D051336:Mitochondrial Membranes / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D010085:Oxidative Phosphorylation; D010539:Permeability
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002308:Cardiolipins; D015525:Fatty Acids, Omega-3; D004281:Docosahexaenoic Acids