Autophagic programmed cell death in Drosophila

Baehrecke, Eric H.

doi:10.1038/sj.cdd.4401280

Cited by 204 publications

(155 citation statements)

References 70 publications

(91 reference statements)

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“…Similar effects also occur in a physiological cell death response that occurs during Drosophila metamorphosis. Steroid regulated death during Drosophila metamorphosis occurs by a process that looks like autophagic cell death (83). However, regulators of the apoptotic machinery such as grim, reaper and dronk control the process (84), and caspase inhibition prevents the death (85).…”

Section: Are Autophagic and Apoptotic Cell Death Different Facets Of mentioning

confidence: 99%

Apoptosis and autophagy: regulatory connections between two supposedly different processes

2007

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Apoptosis and autophagy are genetically-regulated, evolutionarily-conserved processes that regulate cell fate. Both apoptosis and autophagy are important in development and normal physiology and in a wide range of diseases. Recent studies show that despite the marked differences between these two processes, their regulation is intimately connected and the same regulators can sometimes control both apoptosis and autophagy. In this review, I discuss some of these findings, which provide possible molecular mechanisms for crosstalk between apoptosis and autophagy and suggest that it may be useful to think of these processes as different facets of the same cell death continuum rather than completely separate processes. KeywordsAutophagy; Apoptosis; Bcl-2, FADD; Atg 5In the early to mid 1990s there was a rapid increase in our understating about the regulation of apoptosis. Fifteen or so years later we are in the midst of a similarly exciting period for understanding autophagy with very rapid growth of publications on the regulation and function of this process (1). Autophagy (the form of autophagy discussed here is macroautophagy, other forms-microautophagy and chaperone-mediated autophagy share the same lysosomal degradation mechanism but differ in the way that material is delivered to the lysosome) is a degradative process involving sequestration of parts of the cytoplasm in double membrane vesicles (autophagic vesicles or autophagosomes) that fuse with lysosomes forming the autophagolysosome. In the autophagolysosome, the cytoplasmic material that was engulfed is hydrolyzed and the resulting amino acids and other macromolecular precursors can be recycled (2-4), see Fig 1 for a schematic of the process. Autophagy is a mechanism by which organelles are removed and is the primary degradation mechanism for long-lived proteins and thus maintains quality control for proteins and organelles. Autophagy is ubiquitous in eukaryotic cells and important in development and in diverse pathophysiological conditions (5)-for example providing protection against neurodegeneration (6,7), infections (8,9) and tumor development (10-13). Cells that are deficient in autophagy also demonstrate enhanced chromosomal instability (14,15), which may be related to the tumorigenesis associated with autophagy deficiency.Autophagy is important in cell death decisions and can protect cells by preventing them from undergoing apoptosis. For example, increased autophagy in nutrient deprived or growth factorwithdrawn cells allows cell survival (16,17) by inhibiting apoptosis. Autophagy also protects cells from various other apoptotic stimuli (18). It is not clear how autophagy stops cells from undergoing apoptosis; one suggested mechanism is the sequestration of damaged mitochondria (18) thus preventing released cytochrome c from being able to form a functional apoptosome NIH Public Access Autophagic cell death (also known as Type II programmed cell death to distinguish it from apoptosis or Type I programmed cell death) (20-22) has been describ...

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Section: Are Autophagic and Apoptotic Cell Death Different Facets Of mentioning

confidence: 99%

Apoptosis and autophagy: regulatory connections between two supposedly different processes

2007

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“…One type, the so-called 'autophagic cell death' or 'type 2 cell death', is characterized by the appearance of cytoplasmic vacuoles, which are thought to be related to autophagy. 35,36 It should be emphasized that 'autophagy' is a term for a degradation process and not a cell death process. Therefore, 'cell death with autophagy' would be the most appropriate nomenclature for this kind of cell death.…”

Section: Cell Death With Autophagymentioning

confidence: 99%

The pleiotropic role of autophagy: from protein metabolism to bactericide

2005

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Autophagy is in principle a nonselective, bulk degradation system within cells, with a contribution to intracellular protein degradation estimated to be as large as that of the ubiquitin--proteasome system. The primary roles of autophagy are baseline turnover of intracellular proteins and organelles, production of amino acids in nutrient emergency, and regression of retired tissues. These functions guarantee rejuvenation and adaptation to adverse conditions, and even underlie dynamic processes such as development/metamorphosis. In addition, several other roles for autophagy have recently been discovered, such as presentation of endogenous antigens and degradation of invasive bacteria. This review will discuss the biological significance of autophagy from yeast to higher eukaryotes.

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“…7 By contrast, autophagy is a degradative mechanism for long-lived proteins and damaged organelles through the auto-phago-lysosomal pathway and on the other, it provides possibility of self-destruction for cells. 4,5,8 In Drosophila, autophagy can be hormonally controlled by ecdysone; through inhibition of a class-I phosphatidyl-inositol 3-kinase (PI3K) pathway organs, such as the fat body, are eliminated at the end of larval stage. 8,9 MCF-7 cells can also be induced to undergo autophagy and cell death by treatment with the antiestrogen tamoxifen, which increases the intracellular ceramide level and eliminates the inhibitory effect of class-I PI3K pathway.…”

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confidence: 99%

“…4,5,8 In Drosophila, autophagy can be hormonally controlled by ecdysone; through inhibition of a class-I phosphatidyl-inositol 3-kinase (PI3K) pathway organs, such as the fat body, are eliminated at the end of larval stage. 8,9 MCF-7 cells can also be induced to undergo autophagy and cell death by treatment with the antiestrogen tamoxifen, which increases the intracellular ceramide level and eliminates the inhibitory effect of class-I PI3K pathway. 10 Expression of death-associated protein kinase and its death-related protein kinase-1 in MCF-7 and various other cell lines can induce autophagy and caspase-independent cell death.…”

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Clearance of dying autophagic cells of different origin by professional and non-professional phagocytes

et al. 2007

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MCF-7 cells undergo autophagic death upon tamoxifen treatment. Plated on non-adhesive substratum these cells died by anoikis while inducing autophagy as revealed by monodansylcadaverine staining, elevated light-chain-3 expression and electron microscopy. Both de novo and anoikis-derived autophagic dying cells were engulfed by human macrophages and MCF-7 cells. Inhibition of autophagy by 3-methyladenine abolished engulfment of cells dying through de novo autophagy, but not those dying through anoikis. Blocking exposure of phosphatidylserine (PS) on both dying cell types inhibited phagocytosis by MCF-7 but not by macrophages. Gene expression profiling showed that though both types of phagocytes expressed full repertoire of the PS recognition and signaling pathway, macrophages could evolve during engulfment of de novo autophagic cells the potential of calreticulin-mediated processes as well. Our data suggest that cells dying through autophagy and those committing anoikis with autophagy may engage in overlapping but distinct sets of clearance mechanisms in professional and non-professional phagocytes.

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Autophagic programmed cell death in Drosophila

Cited by 204 publications

References 70 publications

Apoptosis and autophagy: regulatory connections between two supposedly different processes

Apoptosis and autophagy: regulatory connections between two supposedly different processes

The pleiotropic role of autophagy: from protein metabolism to bactericide

Clearance of dying autophagic cells of different origin by professional and non-professional phagocytes

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