The roles of phosphoinositides in mammalian autophagy.

Abstract

Autophagy is an evolutionarily conserved cellular process for lysosomal degradation, which is involved in various physiological processes within cells. Its dysfunction is associated with many human diseases, such as cancer, liver diseases, heart diseases, and infectious diseases, including neurodegenerative diseases. Autophagy involves the formation of a double-membrane bound autophagosome and the degradation of cytosolic components via its fusion and maturation with the lysosome. One of the most important steps in the process of autophagy is membrane biogenesis during autophagosome formation/maturation from different membrane sources within cells. However, there is limited knowledge regarding: (1) how the core autophagy machinery is recruited to the initial site to initiate the formation of the isolation membrane and (2) how the autophagosome matures into the functional autolysosome. Lipid supply for nucleation/elongation of the autophagosome has been proposed as one possible mechanism. Accumulating evidence suggests the important role of phosphoinositides as phospholipids, which represent key membrane-localized signals in the regulation of fundamental cellular processes, in autophagosome formation and maturation. This review focuses on how phosphoinositides influence autophagy induction or autophagosome biogenesis/maturation, because the way they are altered by autophagy might contribute to the pathogenesis of human diseases.