Patatin-like phospholipase domain-containing protein 8 (PNPLA8)

Patatin-like phospholipase domain-containing protein 8 (PNPLA8) is a membrane-associated, calcium-independent phospholipase A2 enzyme that catalyzes the cleavage of fatty acids from glycerophospholipids, especially within mitochondrial membranes[1][3]. PNPLA8 facilitates the selective hydrolysis of phospholipids such as phosphatidylethanolamine and phosphatidylcholine, playing a crucial role in mitochondrial lipid metabolism, energy homeostasis, and cellular signaling by generating free fatty acids and lysophospholipids[1][3]. It is highly expressed in the myocardium and is also present in skeletal muscle, brain, liver, pancreas, placenta, and lungs[1]. Mutations or dysfunctions in PNPLA8 are associated with mitochondrial myopathy with lactic acidosis and possibly other disorders featuring defective mitochondrial bioenergetics and increased oxidative stress[3]. Its biological roles include maintaining mitochondrial membrane integrity, modulating apoptosis, and acting in the broader regulation of lipid signaling pathways (notably eicosanoid biosynthesis)[1][3].

Other names

Calcium-independent phospholipase A2-gammaiPLA2-gammaIPLA2GIPLA2-2PNPLA-gammaPLPL8MMLABM-043Intracellular membrane-associated calcium-independent phospholipase A2 gamma

Inhibition of enzymatic activity (for potential PLA2 inhibitors); Modulation of lipid mediator (e.g., arachidonic acid) release