A Mammalian Autophagosome Maturation Mechanism Mediated by TECPR1 and the Atg12-Atg5 Conjugate

Chen, Dandan; Fan, Weiliang; Lu, Yiting; Ding, Xiaojun; Chen, She; Zhong, Qing

doi:10.1016/j.molcel.2011.12.036

Cited by 181 publications

(178 citation statements)

References 62 publications

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“…However the precise relationship between HOPS, EPG5 and ATG14L is still unclear, and needs to be clarified in future studies. Tectonin beta-propeller repeatcontaining 1 (TECPR1) also functions as a tethering factor and we discuss its role further on in the text (Chen et al, 2012).…”

Section: Tethering Factorsmentioning

confidence: 99%

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New insights into autophagosome–lysosome fusion

Nakamura

Yoshimori

2017

Journal of Cell Science

415

324

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Macroautophagy (autophagy) is a highly conserved intracellular degradation system that is essential for homeostasis in eukaryotic cells. Due to the wide variety of the cytoplasmic targets of autophagy, its dysregulation is associated with many diseases in humans, such as neurodegenerative diseases, heart disease and cancer. During autophagy, cytoplasmic materials are sequestered by the autophagosome -a double-membraned structure -and transported to the lysosome for digestion. The specific stages of autophagy are induction, formation of the isolation membrane (phagophore), formation and maturation of the autophagosome and, finally, fusion with a late endosome or lysosome. Although there are significant insights into each of these steps, the mechanisms of autophagosomelysosome fusion are least understood, although there have been several recent advances. In this Commentary, we will summarize the current knowledge regarding autophagosome-lysosome fusion, focusing on mammals, and discuss the remaining questions and future directions of the field.

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Section: Tethering Factorsmentioning

confidence: 99%

“…In addition to the HOPS complex, the PI3P-binding proteinTECPR1 has been suggested to function as a tethering factor in autophagosomal fusion (Chen et al, 2012) (Fig. 4).…”

Section: Phosphoinositides In Autophagosome-lysosome Fusionmentioning

confidence: 99%

New insights into autophagosome–lysosome fusion

Nakamura

Yoshimori

2017

Journal of Cell Science

415

324

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“…However, the exact role of TECPR2 in the autophagy pathway warrants further examination. The fact that TECPR2 shows some similarity to two autophagy-involved proteins -TECPR1 and HPS5 [35,[40][41][42][43] -is expected to shed new light on this issue.…”

Section: Hereditary Spastic Paraparesismentioning

confidence: 99%

Autophagy and human diseases

2013

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Autophagy is a major intracellular degradative process that delivers cytoplasmic materials to the lysosome for degradation. Since the discovery of autophagy-related (Atg) genes in the 1990s, there has been a proliferation of studies on the physiological and pathological roles of autophagy in a variety of autophagy knockout models. However, direct evidence of the connections between ATG gene dysfunction and human diseases has emerged only recently. There are an increasing number of reports showing that mutations in the ATG genes were identified in various human diseases such as neurodegenerative diseases, infectious diseases, and cancers. Here, we review the major advances in identification of mutations or polymorphisms of the ATG genes in human diseases. Current autophagy-modulating compounds in clinical trials are also summarized.

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“…97 At the late stage of autophagy, additional PtdIns3P effectors interact with PtdIns3P. TECPR1 (tectonin b-propeller repeat containing 1), associating with both PtdIns3P and the ATG12-ATG5 complex, mediates the fusion of autophagosomes with lysosomes, 98 whereas FYCO1 (FYVE and coiled-coil domain containing 1) is also involved in the maturation and trafficking of autophagosomes. 17, 99 The stringent requirement of phospholipids in the progression of autophagy points to the indispensable role of their producers, PtdIns3Ks and PI3Ks, in the autophagic pathway.…”

Section: Ptdins3p Is a Key Phospholipid Required For The Progression mentioning

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 Mammalian Autophagosome Maturation Mechanism Mediated by TECPR1 and the Atg12-Atg5 Conjugate

Cited by 181 publications

References 62 publications

New insights into autophagosome–lysosome fusion

New insights into autophagosome–lysosome fusion

Autophagy and human diseases

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

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