The mitochondrial Ca2+-independent phospholipase A2 becomes active in parallel to OPA1 cleavage (760.1)

Accumulation of depolarizing amounts of Ca2+ or Sr2+, as well as chemical uncoupling have been shown to activate a mitochondrial Ca2+-independent phospholipase A2 (iPLA2). Data generated in isolated mitochondria utilizing various electron transport chain inhibitors indicate that neither redox status of particular electron transport chain complexes nor ROS production are primary regulators of the iPLA2; however, loss of membrane potential (∆Ψ) is shared by all of the treatments that produce activation. Therefore, we hypothesized that the iPLA2 is primarily regulated by ∆Ψ. Here we report that the dynamin-like GTPase OPA1 is cleaved from a long form to a short form in parallel to iPLA2 activation. OPA1 cleavage is known to inhibit mitochondrial fusion generating a pool of fragmented mitochondria, which are thereafter targeted for degradation by agents such as PINK1 and Parkin, and for eventual removal by autophagocytosis. Thus, both iPLA2 activation and OPA1 cleavage may contribute to initiating the turnove...