Collection

2016 Nobel Prize in Physiology or Medicine

The 2016 Nobel Prize in Physiology or Medicine has been awarded to Yoshinori Ohsumi, “for his discoveries of mechanisms for autophagy”. To mark the award, we present a Collection of research and review content from Nature Research, including key papers by Professor Ohsumi; our Nature News article also highlights Ohsumi's achievement. Autophagy is the vital process of degradation and recycling of cellular material that supports processes such as development and cell differentiation, and its disruption is linked to diseases including cancer and neurodegenerative disorders. 

Image credit: Image adapted by Emma Carter from Nature Reviews Molecular Cell Biology doi:10.1038/nrm4024

Reviews

Autophagosome biogenesis starts at the isolation membrane (also called the phagophore). Our understanding of the molecular processes that initiate the isolation membrane, the membrane sources from which this membrane originates and how it is expanded to the autophagosome membrane by autophagy-related (ATG) proteins and the vesicular trafficking machinery, is increasing.

Review Article | | Nature Reviews Molecular Cell Biology

Autophagy and apoptosis control the turnover of organelles and proteins within cells, and of cells within organisms, respectively. It is now clear that these processes often occur sequentially, and that crosstalk between the signalling pathways regulating them generally enables autophagy to block the induction of apoptosis, whereas apoptosis-associated caspase activation shuts off autophagy.

Review Article | | Nature Reviews Molecular Cell Biology

Autophagy not only degrades components of host cells but can also target intracellular bacteria and thus contribute to host defences. Here, Huang and Brumell discuss the canonical and selective pathways of antibacterial autophagy, as well as the ways in which bacteria can escape from them and sometimes even use them to promote infection.

Review Article | | Nature Reviews Microbiology

Emerging evidence implicates autophagy in the maintenance of energy homeostasis, both at the cellular level and within the organism as a whole. The authors of this Review discuss the control of cellular autophagy by nutrients, the regulation of energy metabolism by autophagy and the consequences of autophagy dysfunction and modulation in metabolic disease.

Review Article | | Nature Reviews Endocrinology

Autophagy is a beneficial adaptive response to cellular stress, but it can also benefit cancer cells, and can contribute to development of resistance to cancer treatments. The authors describe the complex roles of autophagy and the developments towards modulation of autophagy to improve the effectiveness of prostate cancer therapies.

Review Article | | Nature Reviews Urology

Increasing evidence suggests that autophagy can modulate tissue responses during acute kidney injury, regulate podocyte homeostasis and protect against age-related renal disease. In this Review the authors describe the process of macroautophagy and its role in kidney health, ageing and disease. They also highlight the potential of autophagy as a target for renoprotective therapies.

Review Article | | Nature Reviews Nephrology

Dysfunction of autophagy — an intracellular degradation pathway for cytosolic material — has been implicated in the pathogenesis of various neurodegenerative diseases. Rubinsztein and colleagues review recent progress in this area, focusing on macroautophagy, and discuss how this process may be manipulated to protect against neurodegeneration.

Review Article | | Nature Reviews Neuroscience

Autophagy serves to degrade proteins during starvation. Recent progress has illuminated how, during starvation and nutrient repletion, autophagy can mobilize diverse cellular energy and nutrient stores, such as lipids, carbohydrates and iron, to salvage key metabolites that sustain and facilitate core anabolic functions.

Review Article | | Nature Reviews Molecular Cell Biology

Autophagy underlies the cellular pathology of several rheumatic diseases. Targeting the signalling pathways involved has shown promise in recent clinical trials. Rockel and Kapoor discuss the key regulators involved in autophagy and therapeutic strategies currently in use and under development.

Review Article | | Nature Reviews Rheumatology

Until recently, autophagy, or cellular self-digestion, was thought of primarily as part of the cell's garbage disposal system. Now it is know to be involved in cellular protein and organelle degradation during development as well as during adaptations to changing environmental conditions. Many intriguing questions remain to be answered about this process. For example, how can this one pathway be involved in cytoprotection as well as cell death? What is the connection between autophagy and human disease or ageing? In a review, Mizushima et al. consider recent progress in the field.

Review Article | | Nature

Research

Two papers this week suggest that the process of protein degradation and clearance of cellular components may be more important in maintaining the health of the nervous system than was thought. Both groups show that inhibition of autophagy in mouse brain cells results in neurodegeneration and early death. Autophagy, the protein degradation and recycling of cellular components, is important for the normal growth and development of a cell. The finding that the continual clearance of cellular components is essential for maintaining neuronal health should open up new avenues of research into the nature of neurodegenerative diseases.

Letter | | Nature

Two papers this week suggest that the process of protein degradation and clearance of cellular components may be more important in maintaining the health of the nervous system than was thought. Both groups show that inhibition of autophagy in mouse brain cells results in neurodegeneration and early death. Autophagy, the protein degradation and recycling of cellular components, is important for the normal growth and development of a cell. The finding that the continual clearance of cellular components is essential for maintaining neuronal health should open up new avenues of research into the nature of neurodegenerative diseases.

Letter | | Nature

mTOR inhibition induces autophage-mediated degradation but few mTOR targets in the process have been identified so far. Cecconi and colleagues show that mTOR inhibits the autophagy regulator AMBRA1 by phosphorylation. Following autophagy induction, AMBRA1 is dephosphorylated and interacts with the E3 ligase TRAF6 to stabilize and activate ULK1 (a kinase required for autophagy) through its ubiquitylation.

Article | | Nature Cell Biology

Autophagy initiates with the assembly of a preautophagosomal structure (PAS), triggered by the yeast Atg1 complex. Ohsumi, Noda and colleagues present the crystal structures of Atg13–Atg1 and Atg13–Atg17, revealing how starvation-induced dephosphorylation of Atg13 triggers formationof the Atg1 complex and PAS assembly.

Article | | Nature Structural & Molecular Biology

The core mechanisms of autophagy are generally assumed to be broadly conserved between yeast and mammals. Cheng et al. show that the distribution of PtdIns(3)P between cytoplasmic and luminal leaflets of autophagosomes differs dramatically in yeast and mammalian cells, suggestive of different underlying mechanisms.

Article | | Nature Communications

The endoplasmic reticulum (ER) is a complex network of membranes involved in protein and lipid synthesis, ion homeostasis, protein quality control and organelle communication. It is also a source of membrane-bounded vesicles called autophagosomes, the vehicles for the self-digesting cellular process of autophagy. Two papers published online this week [in this issue of Nature] show how the ER itself is targeted for degradation by autophagy — a process that could ensure constant ER turnover in response to cellular requirements. Ivan Dikic and coworkers find the protein FAM134B is an ER-resident receptor that facilitates 'ER-phagy'. Downregulation of this protein — mutations of which can cause sensory neuropathy in humans — resulted in expanded ER structures and degeneration of mouse sensory neurons. Hitoshi Nakatogawa and colleagues show that the same phenomenon is conserved in yeast, where Atg40 is enriched in the cortical and cytoplasmic ER, loading these ER subdomains into autophagosomes. A further ER-phagy receptor, Atg39, localizes to the perinuclear ER (or the nuclear envelope) and induces autophagic sequestration of a part of the nucleus, thus ensuring cell survival under nitrogen-deprived conditions.

Letter | | Nature