Mammalian macroautophagy at a glance

Abstract

Macroautophagy (referred to here as autophagy) is a process in which cells form double-membrane vesicles, called autophagosomes, around a portion of cytoplasm. These autophagosomes ultimately fuse with lysosomes, resulting in degradation of their contents. Autophagy is upregulated under physiological stress conditions such as starvation. However, mammalian cells undergo autophagy at a basal level that might be important for the clearance of normally occurring, misfolded, ubiquitylated proteins. Autophagy has also been implicated in several human diseases, such as cancer, certain neurodegenerative disorders and infectious diseases. Although autophagy is thought to be predominantly a cell-survival mechanism, some evidence points towards a role in cell death. Our understanding of mammalian autophagy, in terms of the molecular machineries and signalling cascades that are involved in its regulation, has grown considerably over the last few years. In particular, there has been an explosion of data in the last 3 years trying to address the importance of mammalian autophagy in physiology and pathophysiology. Here, we aim to summarise the recent advances in mammalian macroautophagy in terms of its regulation, which will include newly identified molecules and signalling pathways, and we will address the ever-growing roles of autophagy in human physiology and pathology.⇓