ATG16

WD repeat domain phosphoinositide-interacting protein 1 (WIPI) is involved in the lysosomal degradation of cytoplasmic components during starvation-induced autophagy. WIPI1 is a seven bladed beta-propeller protein that provides a scaffold for the assembly of multimeric protein complexes (1). During the assembly of the autophagosome WIPI1 interacts with the lipid phosphatidylinositol-3 phosphate (PI3P) and mediates the recruitment of the large multimeric complex of ATG12-ATG5-ATG16 (1).

Autophagy is an important cellular process that maintains homeostasis by degrading and recycling damaged proteins and organelles. Autophagy receptors, such as p62/SQSTM1, recognize these intracellular cargo and mediate their engulfment by the double-membrane autophagosome. The autophagosomes are subsequently targeted to the lysosome for degradation. An early regulatory step in this process is the activation and lipidation of ATG8 related proteins such as microtubule-associated protein-1 light chain 3 (LC3).

Autophagy is a process by which cells degrade and recycle damaged organelles or misfolded proteins. These various cargo are engulfed in a double-membrane structure called the autophagosome. The autophagosome then fuses with the lysosome to facilitate the degradation of the cargo. This process requires the concerted effort of an extensive network of proteins. One of the early steps of autophagosome assembly is the formation of the large multimeric ATG12-ATG5-ATG16 complex.

Autophagy is an essential cellular process whereby damaged proteins and organelles are degraded and recycled. Autophagy, while happening constantly at a basal level, is tightly regulated and can be further induced under cellular stress. One of the regulators of the early steps of autophagy is ATG4. The ATG4 family of cysteine proteases consists of 4 homologs: ATG4A, ATG4B, ATG4C, and ATG4D.

Autophagy can be broken down into 4 main stages: phagophore nucleation, autophagosome elongation, autophagosome docking and fusion with a lysosome, and vesicle breakdown and degradation. ATG4B is one of four ATG4 homologs (ATG4A, ATG4B, ATG4C, and ATG4D) involved in autophagosome elongation. ATG4B encodes a 48 kDa protein called autophagin-1 that is a member of the C54 family of cysteine proteases.

Autophagy is important for the removal of damaged organelles or proteins as well as for the regulation of cellular homeostasis in response to stress. Proteins or organelles that are targeted for degradation are engulfed in a double-membrane structure called the autophagosome that eventually fuses with the lysosome to mediate cargo degradation. Atg5 plays an important regulatory role in the early steps of this process.

Autophagy is an essential cellular process that maintains homeostasis through the degradation and recycling of cytoplasmic organelles and macromolecules. Substrates targeted for autophagy are engulfed in a double-membrane structure called the autophagosome which is then targeted to the lysosome for degradation. The initiation of autophagy requires two separate ubiquitin-like protein (UBL) systems that regulate autophagosome assembly. In these systems Atg7 acts as an E1-like enzyme for the UBLs Atg12 and Atg8.

Atg12 is a ubiquitin-like protein that plays an essential role in cellular homeostasis by regulating the degradation and recycling of cytoplasmic organelles and macromolecules. Atg12 is one of two ubiquitin-like protein systems that is required during the early steps of autophagosome formation. Upon the initiation of phagopore assembly Atg12 is activated by binding to the E1-like enzyme Atg7 and is then transferred to the E2 enzyme Atg10.

Microtubule-associated protein-1 light chain 3 (LC3/LC3B) is a ubiquitin-like protein involved in the formation of the autophagosome. It is homologous to the yeast Atg8 protein. Autophagosomes are important for the degradation and recycling of intracellular cargo such as misfolded proteins or damaged organelles. Upon induction of autophagy, LC3 is conjugated to the lipid phosphatidylethanolamine (PE) by the Atg12-Atg5-Atg16 protein complex.

ATG9A is the only essential integral membrane protein involved in autophagy. ATG9A contains six transmembrane domains and initiates the assembly of autophagosomes. The autophagosome is a double-membrane structure that engulfs and eventually degrades cytoplasmic materials such as organelles or macromolecules. Assembly of the autophagosome requires the delivery of lipids and membrane components to initiate and expand the double-membrane pre-autophagosome structure called the isolation membrane.