Calcium-independent phospholipase Aγ (iPLAγ) and its roles in cellular functions and diseases.

Calcium-independent phospholipase Aγ (iPLAγ)/patatin-like phospholipase domain-containing lipase 8 (PNPLA8) is one of the iPLA enzymes, which do not require Ca ion for their activity. iPLAγ is a membrane-bound enzyme with unique features, including the utilization of four distinct translation initiation sites and the presence of mitochondrial and peroxisomal localization signals. This enzyme is preferentially distributed in the mitochondria and peroxisomes and is thought to be responsible for the maintenance of lipid homeostasis in these organelles. Thus, both the overexpression and the deletion of iPLAγ in vivo caused mitochondrial abnormalities and dysfunction. Roles of iPLAγ in lipid mediator production and cytoprotection against oxidative stress have also been suggested by in vitro and in vivo studies. The dysregulation of iPLAγ can therefore be a critical factor in the development of many diseases, including metabolic diseases and cancer. In this review, we provide an overview of the biochemical properties of iPLAγ and then summarize the current understanding of the in vivo roles of iPLAγ revealed by knockout mouse studies.