Activation of mitochondrial lysophospholipase by mitochondrial depolarization: role in organelle turnover (758.4)

Abstract

Mitochondria contain a Ca2+‐independent phospholipase A2 (iPLA2) that is activated by loss of membrane potential (ΔΨ). Accumulation of unsaturated fatty acids, determined using heptadecanoic acid as internal standard, was used to quantitate iPLA2 activity. In these incubations, accumulation of saturated fatty acids was also observed. Of interest was whether mitochondria contained lysophospholipase activity and additionally, if activity was regulated similarly to iPLA2 or if appearance of saturated fatty acids was determined simply by lysophospholipid availability. Using 1‐heptadecanoylphosphatidylcholine, 10 mg/mL as substrate and pentadecanoic acid as internal standard it was determined that Percoll purified mitochondria contain lysophospholipase activity that is regulated similarly to iPLA2. When mitochondria are energized, activity is near zero and is up‐regulated when mitochondria are depolarized by a variety of de‐energizing conditions. Fatty acids were released from exogenous and endogenous substrate in nearly equal amounts. At 10 nmol lysophospholipid/mg, there was minimal effect on mitochondrial bioenergetic parameters. Activity is relatively resistant to inhibition by BEL, an inhibitor of iPLA2. Coordinated activation of lipid degrading enzymes by loss of ΔΨ may be involved in the removal of poorly functioning mitochondria by the Parkin/Pink‐1 dependent pathway.