Profiling of fatty acids released during calcium-induced mitochondrial permeability transition in isolated rabbit kidney cortex mitochondria

► Mitochondrial permeability transition (MPT) involves release of fatty acids. ► Some fatty acids released during MPT involve iPLA 2γ. ► iPLA 2γ maintains arachidonic acid homeostasis under normal and stressed conditions. 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 2γ). 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 2γ maintains mitochondrial arachidonic acid homeostasis under both basal and Ca 2+-induced stress conditions.