A current perspective of autophagosome biogenesis

Shibutani, Shusaku; Yoshimori, Tamotsu

doi:10.1038/cr.2013.159

Cited by 315 publications

(265 citation statements)

References 106 publications

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“…2,3,46,47,56 Regulation of autophagy: The core molecular machinery engaged in autophagosome formation, as well as the signaling pathways that stimulate autophagy have been reviewed in detail elsewhere. [57][58][59][60][61] Fifteen autophagy-related (ATG) proteins constitute the core machinery of autophagosome formation. 59 In mammalian cells, these ATG proteins are recruited to form a phagophore, or isolation membrane, which subsequently elongates to form the autophagosome (Figure 2).…”

Section: Autophagy and Ciliummentioning

confidence: 99%

“…Recent studies have shown that phagophore elongation takes place at the endoplasmic reticulum in a structure called the omegasome characterized by the presence of the phosphatidylinositol 3-phosphate binding protein DFCP1. 58,61,62 In addition, other membrane sources also contribute to the biogenesis of the autophagosome, including those of the endosomes and the Golgi apparatus, the contact site between the endoplasmic reticulum and mitochondria, endoplasmic reticulum transition elements, and the plasma membrane (for recent reviews, Lamb et al 58 ; Shibutani and Yoshimori 61 ; and Puri et al 63 ). Each functional module from the initiation of the autophagosome formation to the elongation/closure step involves different ATG proteins.…”

Section: Autophagy and Ciliummentioning

confidence: 99%

“…75 In addition to the maturation of autophagosomes, it is worth noting that SNAREs and elements of the endocytic machinery also contribute to the formation of autophagosomes. 61,71,76 Autophagy and PC. Until recently, the functional interaction between autophagy and PC had not been characterized.…”

Section: Autophagy and Ciliummentioning

confidence: 99%

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Autophagy and regulation of cilia function and assembly

et al. 2014

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Motile and primary cilia (PC) are microtubule-based structures located at the cell surface of many cell types. Cilia govern cellular functions ranging from motility to integration of mechanical and chemical signaling from the environment. Recent studies highlight the interplay between cilia and autophagy, a conserved cellular process responsible for intracellular degradation. Signaling from the PC recruits the autophagic machinery to trigger autophagosome formation. Conversely, autophagy regulates ciliogenesis by controlling the levels of ciliary proteins. The cross talk between autophagy and ciliated structures is a novel aspect of cell biology with major implications in development, physiology and human pathologies related to defects in cilium function. Cell Death and Differentiation (2015) 22, 389-397; doi:10.1038/cdd.2014.171; published online 31 October 2014 FactsAutophagy is a degradative and recycling mechanism that allows cells to adapt to stress situations including nutrient deprivation. Primary cilia (PC) and motile cilia (MC) are sensory structures at the cell surface. PC sense nutrient, growth factor and calcium changes in the extracellular environment and also respond to mechanical stress. MC are beating structures that contribute to innate defense in the lung, for example. The PC is a site for the recruitment of autophagy-related (ATG) proteins that mediate autophagosome formation in response to cilium-dependent signaling. In turn, autophagy regulates the biogenesis of cilia by degrading certain proteins involved in cilia formation. Modulation of autophagy represents a new therapeutic opportunity in diseases related to defective cilia function. Open QuestionsHow are ATG proteins transported to the PC? How do ATG proteins recruited to the PC contribute to the biogenesis of phagophores and autophagosomes? Ciliary proteins are degraded by autophagy. How selective is this degradative pathway? Do some of these proteins contain motifs that result in selective engulfment by autophagosomes?What are the determinants that switch the degradation of ciliary proteins between basal and induced autophagy? Is there any specific function for cilium-dependent autophagy in ciliated cells? Do signals that trigger cilium-dependent autophagy depend on the stimuli (chemical, mechanical) or do all stimuli converge to a single signaling pathway upstream of the autophagy machinery? Can modulation of autophagy contribute to the restoration of cilium functions?Receptors, transporters and specialized plasma membrane structures such as cilia constitute the interfaces between the extracellular and intracellular milieu and allow the cells to trigger specific responses to adapt to changes imposed by the environment. Among these adaptive responses, macroautophagy (hereafter referred to as 'autophagy') is a catabolic process conserved in eukaryotic cells by which the cell recycles its own constituents. 1 Autophagy is involved in the adaptation to starvation, cell differentiation and development, the degradation of aberrant structure...

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Section: Autophagy and Ciliummentioning

confidence: 99%

Section: Autophagy and Ciliummentioning

confidence: 99%

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Autophagy and regulation of cilia function and assembly

et al. 2014

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“…23,26 Activation of the ULK1 complex results in the translocation of the BECN1-containing class III phosphatidylinositol 3-kinase (PtdIns3K) complex to the assembly site of a phagophore 27 to promote the generation of phosphatidylinositol-3-phosphate (PtdIns3P), which is involved in recruiting a number of ATG proteins. 28,29 There are multiple PtdIns3K complexes that, in addition to BECN1, include combinations of the proteins ATG14, SH3GLB1/Bif-1 (SH3-domain GRB2-like endophilin B1), UVRAG (UV radiation resistance associated), and AMBRA1 (autophagy/Beclin 1 regulator 1), as well as the negative regulator KIAA0226/Rubicon; BECN1 can also be prevented from binding the complex due to its interaction with BCL2 (B-cell CLL/lymphoma 2). [30][31][32][33][34] The elongation and expansion of the phagophore involves 2 ubiquitin-like conjugation systems, the ATG12-ATG5-ATG16L1 conjugation system, and the microtubule-associated protein 1 light chain 3 (LC3; Atg8 homolog) conjugation system.…”

Section: The Process and Regulation Of Autophagymentioning

confidence: 99%

ATG16L1: A multifunctional susceptibility factor in Crohn disease

Salem¹,

Ammitzboell²,

Nys³

et al. 2015

Autophagy

110

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“…These proteins can be grouped into various complexes based on their functions: the ULK1 kinase complex, the ATG9-ATG2-WIPI1/Atg18 complex, PIK3C3/Vps34-BECN1-PIK3R4/p150/Vps15 complex, and 2 ubiquitin-like conjugation systems, which include the ATG12-ATG5 and LC3/GABARAP proteins. [5][6][7] In mammalian cells, under autophagy-stimulating conditions, the ULK1 complex (mainly composed of ULK1, ATG13, ATG101 and RB1CC1/FIP200) undergoes a series of phosphorylation/dephosphorylation events, which lead to the activation of this complex and the initiation of autophagy. 8 After the initiation step, a cup-shaped, primary double-membrane structure, the phagophore, is gradually formed.…”

Section: The Process Of Autophagy and Its Machinerymentioning

confidence: 99%

Differential regulatory functions of three classes of phosphatidylinositol and phosphoinositide 3-kinases in autophagy

2015

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Abbreviations: 3-MA, 3-methyladenine; AMBRA1, autophagy/Beclin 1 regulator 1; ATG, autophagy related; ATM, ATM serine/threonine kinase; ATR, ATR serine/threonine kinase; BH3, Bcl-2 homology 3; CCD, coiled-coil domain; CDK, cyclin-dependent kinase; CISD2, CDGSH iron sulfur domain 2; class I/II PI3K, class I/II phosphoinositide 3-kinase; class III PtdIns3K, class III phosphatidylinositol 3-kinase; DAPK1, death-associated protein kinase 1; DDR, DNA damage response; EIF4EBP1, eukaryotic translation initiation factor 4E binding protein 1; ER, endoplasmic reticulum; FOXO, forkhead box O; FYCO1, FYVE and coiledcoil domain containing 1; GAP, GTPase-activating protein; HMGB1, high mobility group box 1; HSPA1A, heat shock 70kDa protein 1A; IR, ionizing radiation; MAPK8, mitogen-activated protein kinase 8; MEFs, mouse embryonic fibroblasts; MTMR, myotubularin-related protein; MTOR, mechanistic target of rapamycin (serine/threonine kinase); MTORC1, mechanistic target of rapamycin complex 1; MVBs, spherical multivesicular bodies; NRBF2, nuclear receptor binding factor 2; PAS, phagophore assembly site; PDPK1, 3-phosphoinositide dependent protein kinase 1; PE, phosphatidylethanolamine; PIKFYVE, phosphoinositide kinase, FYVE finger containing; PINK1, PTEN-induced putative kinase 1; PtdIns3K-C1, class III phosphatidylinositol 3-kinase complex I; PtdIns3K-C2, class III phosphatidylinositol 3-kinase complex II; PKB, protein kinase B; PRKA, protein kinase, AMP-activated; PRKD1, protein kinase D1; PRKDC, protein kinase, DNA-activated, catalytic polypeptide; PtdIns5P, phosphatidylinositol 5-phosphate; PtdIns4P, phosphatidylinositol 4-phosphate; PtdIns(4,5)P 2 , phosphatidylinositol 4,5-bisphosphate; PtdIns3P, phosphatidylinositol 3-phosphate; PtdIns(3,5)P 2 , phosphatidylinositol 3,5-bisphosphate; PtdIns(3,4,5)P 3 , phosphatidylinositol 3,4,5-trisphosphate; RHEB, Ras homolog enriched in brain; RPS6KB1, ribosomal protein S6 kinase, 70kDa, polypeptide 1; SQSTM1, sequestosome 1; TECPR1, tectonin b-propeller repeat containing 1; TFEB, transcription factor EB; TRIM28, tripartite motif containing 28; TSC, tuberous sclerosis; UV, ultraviolet; UVRAG, UV radiation resistance associated; WDFY3, WD repeat and FYVE domain containing 3; WIPI, WD repeat domain, phosphoinositide interacting; ZFYVE1, zinc finger, FYVE domain containing 1.Autophagy is an evolutionarily conserved and exquisitely regulated self-eating cellular process with important biological functions. Phosphatidylinositol 3-kinases (PtdIns3Ks) and phosphoinositide 3-kinases (PI3Ks) are involved in the autophagic process. Here we aim to recapitulate how 3 classes of these lipid kinases differentially regulate autophagy. Generally, activation of the class I PI3K suppresses autophagy, via the well-established PI3K-AKT-MTOR (mechanistic target of rapamycin) complex 1 (MTORC1) pathway. In contrast, the class III PtdIns3K catalytic subunit PIK3C3/Vps34 forms a protein complex with BECN1 and PIK3R4 and produces phosphatidylinositol 3-phosphate (PtdIns3P), which is required for the initiati...

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A current perspective of autophagosome biogenesis

Cited by 315 publications

References 106 publications

Autophagy and regulation of cilia function and assembly

Autophagy and regulation of cilia function and assembly

ATG16L1: A multifunctional susceptibility factor in Crohn disease

Differential regulatory functions of three classes of phosphatidylinositol and phosphoinositide 3-kinases in autophagy

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