title: Profiling of fatty acids released during calcium-induced mitochondrial permeability transition in isolated rabbit kidney cortex mitochondria.
abstract: Increases in intracellular Ca(2+) during cellular stress often lead to the mitochondrial permeability transition (MPT). We examined changes in fatty acids (FAs) released from isolated renal cortical mitochondria subjected to Ca(2+)-induced MPT. Exposing mitochondria to Ca(2+) stimulated mitochondrial swelling and release of FAs such as arachidonic (20:4) and docosahexenoic acids which increased 71% and 32%, respectively, and linoleic (18:2) which decreased 23% compared to controls. Stearic (18:0), oleic (18:1), and linoleic (18:3) acids were unchanged. To elucidate a mechanism for FA release, mitochondria were pre-treated with bromoenolactone (BEL) to inhibit Ca(2+)-independent phospholipase A(2) gamma activity (iPLA(2)γ). BEL blocked Ca(2+)-induced release of arachidonic and behenic (22:0) acids. Finally, four FAs were released in the absence of Ca(2+) in a BEL-sensitive manner, including arachidonic and docosatrienoic acids. Thus, extensive FA release occurs during Ca(2+)-induced MPT, and that mitochondrial iPLA(2)γ maintains mitochondrial arachidonic acid homeostasis under both basal and Ca(2+)-induced stress conditions.
authors: Center for Cell Death, Injury, and Regeneration, Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, Medical University of South Carolina, Charleston, SC 29425, USA.
authors: Jason L
authors: JL
authors: Blum
authors: Gilbert R
authors: GR
authors: Kinsey
authors: Prashant
authors: P
authors: Monian
authors: Bin
authors: B
authors: Sun
authors: Brian S
authors: BS
authors: Cummings
authors: Jane
authors: J
authors: McHowat
authors: Rick G
authors: RG
authors: Schnellmann
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D054522:Group VI Phospholipases A2 / Q000037:antagonists & inhibitors; D006706:Homeostasis / Q000187:drug effects; D007672:Kidney Cortex / Q000187:drug effects*; D019787:Linoleic Acid / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D023421:Models, Animal; D010539:Permeability; D011817:Rabbits
chemical_list: D005227:Fatty Acids; D033681:Mitochondrial Membrane Transport Proteins; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D019787:Linoleic Acid; D054522:Group VI Phospholipases A2; D002118:Calcium