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Autophagy is a catabolic process through which cells replenish their macromolecular stores in response to nutrient deficiency, and also maintain homeostatic health and survival by degrading damaged proteins and organelles. Autophagy has emerged as a fundamental and conserved cellular mechanism with complex roles in health and disease. Nature Cell Biology presents a series of specially commissioned articles that will discuss recent advances and outstanding questions driving this expanding and diverse field. An accompanying online library contains research and Review articles on this topic published in the past two years by Nature Cell Biology and the Nature journals.
An and Harper quantify ribophagy in mammalian cells and show that nutrient-deprivation-induced ribophagy is independent of the ATG8 conjugation system, whereas proteotoxic stress-induced ribophagy requires ATG5 and VPS34.
Selective autophagy is important for controlled degradation of cellular components. However, a selective autophagic degradation mechanism for ribosomes in mammals has remained unclear. A study now describes non-selective and selective ribosome degradation and a significant role for ‘bystander’ non-selective autophagy.
Sato et al. identify ALLO-1 as an autophagy receptor required for paternal organelle clearance in Caenorhabditis elegans, and this process is dependent on ALLO-1 phosphorylation by the TBK1 family kinase IKKE-1.
Lu et al. show that the choice between proteasomal degradation and selective autophagy is independent of the ubiquitin-binding properties of the receptors but largely determined by oligomerization potential.
Fumagalli et al. show that Sec62 delivers ER components to the autolysosome for clearance by acting as a receptor for autophagy protein LC3-II. This identifies Sec62 as a critical factor for selective ER turnover.
The endoplasmic reticulum (ER) is the largest membrane-bound organelle in cells, and its size needs to be carefully controlled. Downsizing the ER by autophagy is now shown to involve Sec62, a protein that also helps to build up the organelle. This link suggests a molecular switch for ER size control.
De Leo et al. identify a lysosomal response to autophagic cargo during lysosome–autophagosome fusion that involves TLR9 activation and OCRL recruitment, and leads to a regulated local increase in PtdIns(4,5)P2, which is necessary for a normal autophagic flux.
Jiang et al. show that Disabled-2 (Dab2) regulates the switch between autophagy and apoptosis in TGB-β-treated cells, through regulation of the Beclin-1–Vps34 interaction.
In this Review, Prinz and co-authors discuss the role of the endoplasmic reticulum (ER) in the de novo generation of peroxisomes, lipid droplets and omegasomes, and how this requires subdomains with specific protein and lipid compositions.
Orhon et al. report that primary-cilium-mediated fluid flow sensing triggers autophagy through LKB1–AMPK–mTOR signalling, and thereby controls the volume of kidney epithelial cells.
The primary cilium and the process of autophagy are thought to be in a functionally reciprocal relationship. In further support of this link, fluid flow sensing by the primary cilium is now shown to induce autophagy, which in turn regulates the volume of kidney epithelial cells.
Green and colleagues characterize LC3-associated phagocytosis as a process that depends on Rubicon, Beclin-1, UVRAG and VPS34 but not on canonical autophagy proteins.
Phagocytic cells engulf their prey into vesicular structures called phagosomes, of which a certain proportion becomes demarcated for enhanced maturation by a process called LC3-associated phagocytosis (LAP). Light has now been shed on the molecular requirements of LAP, establishing a central role for the protein Rubicon in the immune response to Aspergillus fumigatus.
Ding and colleagues show that somatic cell reprogramming does not depend on Atg5-dependent canonical autophagy, but requires mitochondrial clearance in an Atg5-independent manner downstream of AMPK.