Showing papers on "Autophagosome membrane published in 2013"

The autophagosome: origins unknown, biogenesis complex

Abstract: 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.

The Atg8 family: multifunctional ubiquitin-like key regulators of autophagy.

Abstract: 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.

Autophagy as a defence against intracellular pathogens.

Abstract: Autophagy is a membrane trafficking pathway that results in the formation of autophagosomes which deliver portions of the cytosol to lysosomes for degradation. When autophagosomes engulf intracellular pathogens, the pathway is called 'xenophagy' because it leads to the removal of foreign material. Autophagy is activated during infection by Toll-like receptors that recognize pathogen-associated molecular patterns. This allows autophagy to kill micro-organisms and present pathogen components to the innate and acquired immune systems. The targeting of pathogens by autophagy is selective and involves a growing family of autophagy receptors that bind to the autophagosome membrane protein LC3 (light-chain 3)/Atg8 (autography-related protein 8). Ubiquitination of microbes identifies them as substrates for autophagy and they are delivered to autophagosomes by autophagy receptors that bind both ubiquitin and LC3/Atg8. Bacteria can also be detected before they enter the cytosol by autophagy receptors that scan the surface of membrane compartments for evidence of damage. The observation that some pathogens survive in cells suggests they can evade complete destruction by autophagy. For some bacteria this involves proteins that shield the surface of the bacteria from recognition by autophagy receptors. Other viruses and bacteria are resistant to degradation in lysosomes and use autophagosomes and/or lysosomes as sites for replication. Most of our current understanding of the role played by autophagy during microbial infection has come from studies of bacteria and viruses in tissue culture cell lines. Future work will focus on understanding how autophagy determines the outcome of infection 'in vivo', and how autophagy pathways can be exploited therapeutically.

Current views on the source of the autophagosome membrane

Abstract: Autophagy was discovered in the late 1950s when scientists using the first electron microscopes saw membrane-bound structures in cells that contained cytoplasmic organelles, including mitochondria. Pursuant to further morphological characterization it was recognized that these vesicles, now called autophagosomes, are found in all eukaryotic cells and undergo changes in morphology from a double-membraned vesicle with recognizable content, i.e. sequestered organelles, to a uniformly dense core autolysosome. Genetic screens in the yeast Saccharomyces cerevisiae in the 1990s provided a molecule framework for the next era of discovery during which the interest in, and research into, autophagy has rapidly expanded into many areas of human biology and disease. A relatively small cohort of approximately 36 proteins, called Atgs (autophagy-related proteins), orchestrate the formation of the autophagosome, and these are now being studied and functionally characterized. Although the function of these proteins is being elucidated, the underlying molecular mechanisms of how autophagosomes form are still not completely understood. Recent advances have, however, provided a significant advance in both our understanding of the molecular control of the Atg proteins and the source of the membranes. A consensus view is emerging from these advances that the endoplasmic reticulum is the nucleation site for the autophagosome, and that contributions from other compartments (Golgi, endosomes and plasma membrane) are required. In the present chapter, I review the data from the pre-molecular decades, and discuss the most recent publications to give an overview of the current view of where, and how, autophagosomes form in mammalian cells.

Autophagy of Chloroplasts During Leaf Senescence

Abstract: During leaf senescence, chloroplasts undergo the programmed breakdown of both stromal and thylakoid components of the photosynthetic apparatus. This strategy has evolved to remobilize nutrients from old leaves into newly developing tissues and sustain maximal growth rates. After the remobilization of chloroplast components, some shrunken chloroplasts called gerontoplasts, which are plastid structures formed by the loss of the thylakoid membrane network, remain in the cytoplasm. Concomitantly, the population of chloroplasts is decreased in mesophyll cells. The morphological traits of senescing cells, including the capture of whole chloroplasts in the vacuole has been observed by electron microscopy since the early 1980s. Chloroplast degradation in the vacuole has been observed.

Autophagy: Pinpointing the mysterious membrane donors

Abstract: Whether the autophagosomal membrane is derived from the endoplasmic reticulum (ER), mitochondria or the plasma membrane has been controversial. Here, Hamasaki et al. find that, in mammalian cells, autophagosomes originate at ER–mitochondrion contact sites. During starvation the pre-autophagosome marker ATG14 accumulated at ER–mitochondrion contact sites, and, similarly, co-fractionated with mitochondrion-associated ER membranes (which contain the contact sites). Moreover, ATG5, which is involved in autophagosome elongation and closure, also localized at ER–mitochondrion contact sites. Interestingly, knockdown of the ER SNARE protein STX17 during starvation hindered the localization of ATG14 specifically at these contact sites and decreased autophagy, indicating a crucial role for STX17-dependent ATG14 recruitment in autophagosome formation. The finding that ER–mitochondrion contact sites act as autophagosome membrane donors explains why previous studies had obtained evidence for both the ER and mitochondria in this process.