Glycogen autophagosomes in polymorphonuclear leukocytes induced by rickettsiae

Rikihisa, Yasuko

doi:10.1002/ar.1092080302

Cited by 69 publications

(44 citation statements)

References 16 publications

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“…The molecular basis of autophagy was first connected to human diseases by Beth Levine's laboratory through the identification of BECN1/VPS30/ ATG6 as a tumor suppressor gene [25]. Subsequently, a series of studies uncovered the connections between autophagy and pathophysiological conditions, such as pathogen infection [26][27][28][29] and neurodegeneration [30], and its dual role in cell growth and death [31,32].…”

Section: The History Of Discoverymentioning

confidence: 99%

The machinery of macroautophagy

et al. 2013

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Autophagy is a primarily degradative pathway that takes place in all eukaryotic cells. It is used for recycling cytoplasm to generate macromolecular building blocks and energy under stress conditions, to remove superfluous and damaged organelles to adapt to changing nutrient conditions and to maintain cellular homeostasis. In addition, autophagy plays a critical role in cytoprotection by preventing the accumulation of toxic proteins and through its action in various aspects of immunity including the elimination of invasive microbes and its participation in antigen presentation. The most prevalent form of autophagy is macroautophagy, and during this process, the cell forms a double-membrane sequestering compartment termed the phagophore, which matures into an autophagosome. Following delivery to the vacuole or lysosome, the cargo is degraded and the resulting macromolecules are released back into the cytosol for reuse. The past two decades have resulted in a tremendous increase with regard to the molecular studies of autophagy being carried out in yeast and other eukaryotes. Part of the surge in interest in this topic is due to the connection of autophagy with a wide range of human pathophysiologies including cancer, myopathies, diabetes and neurodegenerative disease. However, there are still many aspects of autophagy that remain unclear, including the process of phagophore formation, the regulatory mechanisms that control its induction and the function of most of the autophagy-related proteins. In this review, we focus on macroautophagy, briefly describing the discovery of this process in mammalian cells, discussing the current views concerning the donor membrane that forms the phagophore, and characterizing the autophagy machinery including the available structural information.

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Section: The History Of Discoverymentioning

confidence: 99%

The machinery of macroautophagy

et al. 2013

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“…That autophagy could contribute to cellular clearance of microbes was evident already in the 1980s, 31 but it was first a decade later that the molecular tools to study autophagy in immune responses became available. More recently, autophagy has been shown in a number of cases to contribute to defenses against microbial invasion.…”

Section: Autophagy In Immunitymentioning

confidence: 99%

Role of autophagy in disease resistance and hypersensitive response-associated cell death

Hofius

Munch²,

Bressendorff³

et al. 2011

Cell Death Differ

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Ancient autophagy pathways are emerging as key defense modules in host eukaryotic cells against microbial pathogens. Apart from actively eliminating intracellular intruders, autophagy is also responsible for cell survival, for example by reducing the deleterious effects of endoplasmic reticulum stress. At the same time, autophagy can contribute to cellular suicide. The concurrent engagement of autophagy in these processes during infection may sometimes mask its contribution to differing pro-survival and pro-death decisions. The importance of autophagy in innate immunity in mammals is well documented, but how autophagy contributes to plant innate immunity and cell death is not that clear. A few research reports have appeared recently to shed light on the roles of autophagy in plant-pathogen interactions and in disease-associated host cell death. We present a first attempt to reconcile the results of this research. Cell Death and Differentiation (2011) 18, 1257-1262 doi:10.1038/cdd.2011 published online 29 April 2011 Autophagy mediates the degradation of bulk proteins and is also involved in the clearance of damaged organelles, insoluble protein aggregates and lipids. 1-3 Autophagic digestion and recycling can occur as a survival mechanism to maintain cellular homeostasis and to respond to environmental stresses, such as nutrient depletion or pathogen attack, but may also function as a mediator and/or mechanism of programmed cell death. [4][5][6][7][8] Several subtypes of autophagy are described, but macroautophagy (hereafter termed autophagy) is the most extensively studied 9 and will be the only form described here. The process is characterized by the formation of large, double-membrane vesicles called autophagosomes. These structures arise from expanding single membranes (termed phagophores), which enclose cytoplasmic material and organelles for degradation. Completed autophagosomes fuse with the vacuole/lysosome to release the inner singlemembrane vesicle, called the autophagic body, into the lumen for hydrolytic degradation and recycling. 2,10 The mechanism of autophagy is conserved in yeast, plants and metazoans, and involves the action of canonical autophagy related genes (ATG) that synthesize and coordinate membrane rearrangements to allow cellular catabolism. 1,2 The core sets of ATG genes seem to be present in all eukaryotes and to be essential for the autophagy pathway (Figure 1). For instance, induction of autophagy requires the negative regulator target of rapamycin (TOR) kinase and the ATG1 kinase complex, which control the activity of the phosphatidylinositol 3-kinase complex containing, for example, ATG6/Beclin1. 11 Initiation and completion of autophagosome formation involves two ubiquitin-like conjugation systems to produce ATG12-ATG5 and ATG8-phosphatidylethanolamine (ATG8-PE) conjugates. ATG8-PE conjugation involves the cysteine proteinase ATG4 and the E1-like protein ATG7, and lipidated ATG8 is linked to and translocated with autophagosomes to the vacuole. 12 Therefore, conversion from solu...

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“…Autophagy has been also observed in obligatory intracellular bacterial infection, including Rickettsia conorii (7) and Orientia (former R.) tsutsugamushi (8). We have been studying the role of autophagy in Anaplasma phagocytophilum (Ap) infection.…”

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confidence: 99%

Autophagosomes induced by a bacterial Beclin 1 binding protein facilitate obligatory intracellular infection

Niu

Xiong

Yamamoto

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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137

160

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Autophagy, a cytoplasmic catabolic process, plays a critical role in defense against intracellular infection. In turn, evasion or inhibition of autophagy has emerged as an important virulence factor for intracellular pathogens. However, Anaplasma phagocytophilum , the obligatory intracellular bacterium that causes human granulocytic anaplasmosis, replicates in the membrane-bound compartment resembling early autophagosome. Here, we found that Anaplasma translocated substrate 1 (Ats-1), a type IV secretion effector, binds Beclin 1, a subunit of the class III PI3K and Atg14L, and it nucleates autophagosomes with markers of omegasomes, double FYVE-containing protein 1, Atg14L, and LC3. Ats-1 autophagy induction did not activate the starvation signaling pathway of mammalian target of rapamycin. These autophagy proteins were also localized to the Anaplasma inclusion. Ectopically expressed Ats-1 targeted the Anaplasma inclusions and enhanced infection, whereas host cytoplasmic delivery of anti–Ats-1 or Beclin 1 depletion by siRNA suppressed the infection; beclin 1 heterozygous-deficient mice were resistant to Anaplasma infection. Furthermore, Anaplasma growth arrest by the class III PI3K inhibitor 3-methyladenine was alleviated by essential amino acid supplementation. Thus, Anaplasma actively induces autophagy by secreting Ats-1 that hijacks the Beclin 1-Atg14L autophagy initiation pathway likely to acquire host nutrients for its growth.

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Glycogen autophagosomes in polymorphonuclear leukocytes induced by rickettsiae

Cited by 69 publications

References 16 publications

The machinery of macroautophagy

The machinery of macroautophagy

Role of autophagy in disease resistance and hypersensitive response-associated cell death

Autophagosomes induced by a bacterial Beclin 1 binding protein facilitate obligatory intracellular infection

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