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Cold Spring Harbor Perspectives in... May 2014Autophagy is a lysosome-mediated degradative system that is a highly conserved pathway present in all eukaryotes. In all cells, double-membrane autophagosomes form and... (Review)
Review
Autophagy is a lysosome-mediated degradative system that is a highly conserved pathway present in all eukaryotes. In all cells, double-membrane autophagosomes form and engulf cytoplasmic components, delivering them to the lysosome for degradation. Autophagy is essential for cell health and can be activated to function as a recycling pathway in the absence of nutrients or as a quality-control pathway to eliminate damaged organelles or even to eliminate invading pathogens. Autophagy was first identified as a pathway in mammalian cells using morphological techniques, but the Atg (autophagy-related) genes required for autophagy were identified in yeast genetic screens. Despite tremendous advances in elucidating the function of individual Atg proteins, our knowledge of how autophagosomes form and subsequently interact with the endosomal pathway has lagged behind. Recent progress toward understanding where and how both the endocytotic and autophagic pathways overlap is reviewed here.
Topics: Animals; Autophagy; Endocytosis; Endosomes; Humans; Lysosomes; Phagosomes; SNARE Proteins
PubMed: 24789822
DOI: 10.1101/cshperspect.a018358 -
Nature Reviews. Microbiology Feb 2014Autophagy is a cellular process that targets proteins, lipids and organelles to lysosomes for degradation, but it has also been shown to combat infection with various... (Review)
Review
Autophagy is a cellular process that targets proteins, lipids and organelles to lysosomes for degradation, but it has also been shown to combat infection with various pathogenic bacteria. In turn, bacteria have developed diverse strategies to avoid autophagy by interfering with autophagy signalling or the autophagy machinery and, in some cases, they even exploit autophagy for their growth. In this Review, we discuss canonical and non-canonical autophagy pathways and our current knowledge of antibacterial autophagy, with a focus on the interplay between bacterial factors and autophagy components.
Topics: Autophagy; Bacteria; Host-Pathogen Interactions; Lysosomes; Phagocytosis; Phagosomes
PubMed: 24384599
DOI: 10.1038/nrmicro3160 -
Methods (San Diego, Calif.) Mar 2015Xenophagy is an autophagic phenomenon that specifically involves pathogens and other non-host entities. Although the understanding of the relationship between...
Xenophagy is an autophagic phenomenon that specifically involves pathogens and other non-host entities. Although the understanding of the relationship between autophagosomes and invading organisms has grown significantly in the past decade, the exact steps to confirm xenophagy has been not been thoroughly defined. Here we describe a methodical approach to confirming autophagy, its interaction with bacterial invasion, as well as the specific type of autophagic formation (i.e. autophagosome, autolysosome, phagolysosome). Further, we argue that xenophagy is not limited to pathogen interaction with autophagosome, but also non-microbial entities such as iron.
Topics: Autophagy; Brucella; Host-Pathogen Interactions; Humans; Infections; Lysosomes; Molecular Biology; Phagosomes
PubMed: 25497060
DOI: 10.1016/j.ymeth.2014.12.005 -
EMBO Reports Aug 2014Autophagy is the main cellular catabolic process responsible for degrading organelles and large protein aggregates. It is initiated by the formation of a unique membrane... (Review)
Review
Autophagy is the main cellular catabolic process responsible for degrading organelles and large protein aggregates. It is initiated by the formation of a unique membrane structure, the phagophore, which engulfs part of the cytoplasm and forms a double-membrane vesicle termed the autophagosome. Fusion of the outer autophagosomal membrane with the lysosome and degradation of the inner membrane contents complete the process. The extent of autophagy must be tightly regulated to avoid destruction of proteins and organelles essential for cell survival. Autophagic activity is thus regulated by external and internal cues, which initiate the formation of well-defined autophagy-related protein complexes that mediate autophagosome formation and selective cargo recruitment into these organelles. Autophagosome formation and the signaling pathways that regulate it have recently attracted substantial attention. In this review, we analyze the different signaling pathways that regulate autophagy and discuss recent progress in our understanding of autophagosome biogenesis.
Topics: Animals; Autophagy; Energy Metabolism; Humans; Microtubule-Associated Proteins; Oxidation-Reduction; Phagosomes; Signal Transduction; Vesicular Transport Proteins
PubMed: 25027988
DOI: 10.15252/embr.201439076 -
Cell Research Jan 2014
Topics: Animals; Autophagy; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Humans; Phagosomes
PubMed: 24384820
DOI: 10.1038/cr.2014.1 -
Seminars in Cell & Developmental Biology Sep 2010Macroautophagy (hereafter autophagy) is a cellular degradation process, which in yeast is induced in response to nutrient deprivation. In this process, a double-membrane... (Review)
Review
Macroautophagy (hereafter autophagy) is a cellular degradation process, which in yeast is induced in response to nutrient deprivation. In this process, a double-membrane vesicle, an autophagosome, surrounds part of the cytoplasm and fuses with the vacuole to allow the breakdown and subsequent recycling of the cargo. In yeast, many autophagy-related (ATG) genes have been identified that are required for selective and/or nonselective autophagy. In all autophagy-related pathways, core Atg proteins are required for the formation of the autophagosome, which is one of the most unique aspects of autophagy and is unlike other vesicle transport events. In contrast to nonselective autophagy, the selective processes are induced in response to various specific physiological conditions such as alterations in the carbon source. In this review, we provide an overview of the common aspects concerning the mechanism of autophagy-related pathways, and highlight recent advances in our understanding of the machinery that controls autophagy induction in response to nutrient starvation conditions.
Topics: Autophagy; Phagosomes; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Signal Transduction
PubMed: 20359542
DOI: 10.1016/j.semcdb.2010.03.009 -
Autophagy Jul 2013Autophagy is an evolutionarily conserved cellular process through which long-lived proteins and damaged organelles are recycled to maintain energy homeostasis. These... (Review)
Review
Autophagy is an evolutionarily conserved cellular process through which long-lived proteins and damaged organelles are recycled to maintain energy homeostasis. These proteins and organelles are sequestered into a double-membrane structure, or autophagosome, which subsequently fuses with a lysosome in order to degrade the cargo. Although originally classified as a type of programmed cell death, autophagy is more widely viewed as a basic cell survival mechanism to combat environmental stressors. Autophagy genes were initially identified in yeast and were found to be necessary to circumvent nutrient stress and starvation. Subsequent elucidation of mammalian gene counterparts has highlighted the importance of this process to normal development. This review provides an overview of autophagy, the types of autophagy, its regulation and its known impact on development gleaned primarily from murine models.
Topics: Animals; Apoptosis; Autophagy; Growth and Development; Humans; Models, Biological; Phagosomes; Stress, Physiological
PubMed: 24121596
DOI: 10.4161/auto.24273 -
The Journal of Cell Biology Oct 2001Phosphoinositide 3 kinases (PI3Ks)*Abbreviation used in this paper: PI3K, phosphoinositide 3 kinase. are known as regulators of phagocytosis. Recent results demonstrate...
Phosphoinositide 3 kinases (PI3Ks)*Abbreviation used in this paper: PI3K, phosphoinositide 3 kinase. are known as regulators of phagocytosis. Recent results demonstrate that class I and III PI3Ks act consecutively in phagosome formation and maturation, and that their respective products, phosphatidylinositol 3,4,5-trisphosphate (PI[3,4,5]P(3)) and phosphatidylinositol 3-phosphate (PI[3]P), accumulate transiently at different stages. Phagosomes containing Mycobacterium tuberculosis do not acquire the PI(3)P-binding protein EEA1, which is required for phagosome maturation. This suggests a possible mechanism of how this microorganism evades degradation in phagolysosomes.
Topics: Humans; Immunoglobulin G; Membrane Proteins; Models, Biological; Molecular Structure; Mycobacterium tuberculosis; Phagocytes; Phagocytosis; Phagosomes; Phosphatidylinositol 3-Kinases; Phosphatidylinositol Phosphates; Vesicular Transport Proteins
PubMed: 11581282
DOI: 10.1083/jcb.200109001 -
Biochimica Et Biophysica Acta.... Sep 2017Phagocytosis is an essential mechanism through which innate immune cells ingest foreign material that is either destroyed or used to generate and present antigens and... (Review)
Review
Phagocytosis is an essential mechanism through which innate immune cells ingest foreign material that is either destroyed or used to generate and present antigens and initiate adaptive immune responses. While a role for the ER during phagosome biogenesis has been recognized, whether fusion with ER cisternae or vesicular derivatives occurs has been the source of much contention. Membrane contact sites (MCS) are tight appositions between ER membranes and various organelles that coordinate multiple functions including localized signalling, lipid transfer and trafficking. The discovery that MCS form between the ER and phagosomes now begs the question of whether MCS play a role in connecting the ER to phagosomes under different contexts. In this review, we consider the implications of MCS between the ER and phagosomes during cross-presentation and infection with intracellular pathogens. We also discuss the similarities between these contacts and those between the ER and plasma membrane and acidic organelles such as endosomes and lysosomes. This article is part of a Special Issue entitled: Membrane Contact Sites edited by Christian Ungermann and Benoit Kornmann.
Topics: Animals; Calcium Signaling; Endoplasmic Reticulum; Humans; Membrane Fusion; Phagosomes
PubMed: 28432021
DOI: 10.1016/j.bbamcr.2017.04.007 -
Communications Biology Oct 2023Phagosome maturation is critical for immune defense, defining whether ingested material is destroyed or converted into antigens. Sec22b regulates phagosome maturation,...
Phagosome maturation is critical for immune defense, defining whether ingested material is destroyed or converted into antigens. Sec22b regulates phagosome maturation, yet how has remained unclear. Here we show Sec22b tethers endoplasmic reticulum-phagosome membrane contact sites (MCS) independently of the known tether STIM1. Sec22b knockdown increases calcium signaling, phagolysosome fusion and antigen degradation and alters phagosomal phospholipids PI(3)P, PS and PI(4)P. Levels of PI(4)P, a lysosome docking lipid, are rescued by Sec22b re-expression and by expression of the artificial tether MAPPER but not the MCS-disrupting mutant Sec22b-P33. Moreover, Sec22b co-precipitates with the PS/PI(4)P exchange protein ORP8. Wild-type, but not mutant ORP8 rescues phagosomal PI(4)P and reduces antigen degradation. Sec22b, MAPPER and ORP8 but not P33 or mutant-ORP8 restores phagolysosome fusion in knockdown cells. These findings clarify an alternative mechanism through which Sec22b controls phagosome maturation and beg a reassessment of the relative contribution of Sec22b-mediated fusion versus tethering to phagosome biology.
Topics: Phagosomes; Phagocytosis; Endoplasmic Reticulum; Phosphatidylinositol Phosphates
PubMed: 37794132
DOI: 10.1038/s42003-023-05382-0