Macroautophagy (‘autophagy’), is the process by which cells can form a double-membraned vesicle that encapsulates material to be degraded by the lysosome. This can include complex structures such as damaged mitochondria, peroxisomes, protein aggregates and large swathes of cytoplasm that can not be processed efficiently by other means of degradation. Recycling of amino acids and lipids through autophagy allows the cell to form intracellular pools that aid survival during periods of stress, including growth factor deprivation, amino acid starvation or a depleted oxygen supply. One of the major functions of autophagy that has emerged over the last decade is its importance as a safeguard against infection. The ability of autophagy to selectively target intracellular pathogens for destruction is now regarded as a key aspect of the innate immune response. However, pathogens have evolved mechanisms to either evade or reconfigure the autophagy pathway for their own survival. Understanding how pathogens interact with and manipulate the host autophagy pathway will hopefully provide a basis for combating infection and increase our understanding of the role and regulation of autophagy. Herein, we will discuss how the host cell can identify and target invading pathogens and how pathogens have adapted in order to evade destruction by the host cell. In particular, we will focus on interactions between the mammalian autophagy gene 8 (ATG8) proteins and the host and pathogen effector proteins.

Autophagy is an evolutionarily-conserved catabolic process initiated by the engulfment of cytosolic components in a crescent-shaped structure, called the phagophore, that expands and fuses to form a closed double-membrane vesicle, the autophagosome. Autophagosomes are subsequently targeted to the lysosome/vacuole with which they fuse to degrade their content. The formation of the autophagosome is carried out by a set of autophagy-related proteins (Atg), highly conserved from yeast to mammals. The Atg8s are Ubl (ubiquitin-like) proteins that play an essential role in autophagosome biogenesis. This family of proteins comprises a single member in yeast and several mammalian homologues grouped into three subfamilies: LC3 (light-chain 3), GABARAP (γ-aminobutyric acid receptor-associated protein) and GATE-16 (Golgi-associated ATPase enhancer of 16 kDa). The Atg8s are synthesized as cytosolic precursors, but can undergo a series of post-translational modifications leading to their tight association with autophagosomal structures following autophagy induction. Owing to this feature, the Atg8 proteins have been widely served as key molecules to monitor autophagosomes and autophagic activity. Studies in both yeast and mammalian systems have demonstrated that Atg8s play a dual role in the autophagosome formation process, coupling between selective incorporation of autophagy cargo and promoting autophagosome membrane expansion and closure. The membrane-remodelling activity of the Atg8 proteins is associated with their capacity to promote tethering and hemifusion of liposomes in vitro .