Impacts of P4-ATPase Deletion on Membrane Asymmetry and Disease Development

Phospholipids exhibit an asymmetrical distribution on the cell membrane. P4-ATPases, type IV lipid flippases, are responsible for establishing and maintaining this phospholipid compositional asymmetry. The essential beta subunit CDC50 (also known as TMEM30) assists in the transport and proper functioning of P4-ATPases. Deletion of P4-ATPases and its beta subunit disrupts the membrane asymmetry, impacting the growth and development and leading to various diseases affecting the nervous, skeletal muscle, digestive, and hematopoietic systems. This review discusses the crucial roles of P4-ATPases and their beta subunit in Saccharomyces cerevisiae, Arabidopsis thaliana, Caenorhabditis elegans, and mammals, offering valuable insights for future research. Phospholipid flippases are essential enzymes involved in the maintenance and regulation of the membrane phospholipid bilayer structure. They preserve the cell membrane asymmetry and participate in cell signaling, cell membrane transport, and vesicle formation. Studies on lipid flippases have enhanced our understanding of the fundamental biological processes of cell membranes and provided new directions for the diagnosis and treatment of various diseases. This review explores the roles of phospholipid-flipping enzymes in various species to provide a theoretical basis for future research.