A missing piece of the puzzle: Atg11 functions as a scaffold to activate Atg1 for selective autophagy

The mechanism regulating Atg1 kinase activity for the initiation of selective macroautophagy (hereafter autophagy) under nutrient-rich conditions has been a long-standing question. Canonically in yeast, nutrient starvation or rapamycin treatment repress TOR complex 1 and stimulate the Atg1 complex (including at least Atg1, Atg13, Atg17, Atg29 and Atg31), which allows the recruitment of downstream autophagy-related (Atg) components to the phagophore assembly site (PAS), culminating in phagophore formation, and, subsequently, autophagosome biogenesis. Atg1 also functions under conditions promoting selective autophagy that do not necessarily require nutrient deprivation for induction. However, there has been some debate as to whether Atg1 catalytic activity plays a more important role under conditions of nutrient starvation-induced autophagy (i.e., bulk autophagy) vs. selective autophagy (e.g., the cytoplasm-to-vacuole targeting [Cvt] pathway). A recent paper by Kamber and colleagues investigates the mechanism regulating Atg1 activity during selective autophagy.

[1]  Vladimir Denic,et al.  Receptor-Bound Targets of Selective Autophagy Use a Scaffold Protein to Activate the Atg1 Kinase. , 2015, Molecular cell.

[2]  Y. Fujioka,et al.  Atg1 family kinases in autophagy initiation , 2015, Cellular and Molecular Life Sciences.

[3]  D. Klionsky,et al.  The yeast Saccharomyces cerevisiae: an overview of methods to study autophagy progression. , 2015, Methods.

[4]  D. Klionsky,et al.  Regulation of autophagy: Modulation of the size and number of autophagosomes , 2014, FEBS letters.

[5]  A. Motley,et al.  Deficiency of the exportomer components Pex1, Pex6, and Pex15 causes enhanced pexophagy in Saccharomyces cerevisiae , 2014, Autophagy.

[6]  Leon H. Chew,et al.  Atg29 phosphorylation regulates coordination of the Atg17-Atg31-Atg29 complex with the Atg11 scaffold during autophagy initiation , 2013, Proceedings of the National Academy of Sciences.

[7]  T. P. Neufeld,et al.  ULK1 induces autophagy by phosphorylating Beclin-1 and activating Vps34 lipid kinase , 2013, Nature Cell Biology.

[8]  Kay Hofmann,et al.  Binding of the Atg1/ULK1 kinase to the ubiquitin‐like protein Atg8 regulates autophagy , 2012, The EMBO journal.

[9]  A. Motley,et al.  Pex3-anchored Atg36 tags peroxisomes for degradation in Saccharomyces cerevisiae , 2012, The EMBO journal.

[10]  Gustav Ammerer,et al.  Activation of Atg1 kinase in autophagy by regulated phosphorylation , 2010, Autophagy.

[11]  Y. Ohsumi,et al.  Selective transport of alpha-mannosidase by autophagic pathways: identification of a novel receptor, Atg34p. , 2010, The Journal of biological chemistry.

[12]  Yuh-Ying Yeh,et al.  Autophosphorylation Within the Atg1 Activation Loop Is Required for Both Kinase Activity and the Induction of Autophagy in Saccharomyces cerevisiae , 2010, Genetics.

[13]  A. Burlingame,et al.  Chemical Genetic Approach for Kinase‐Substrate Mapping by Covalent Capture of Thiophosphopeptides and Analysis by Mass Spectrometry , 2010, Current protocols in chemical biology.

[14]  Tatsuo Fukagawa,et al.  An auxin-based degron system for the rapid depletion of proteins in nonplant cells , 2009, Nature Methods.

[15]  D. Klionsky,et al.  In vivo reconstitution of autophagy in Saccharomyces cerevisiae , 2008, The Journal of cell biology.

[16]  D. Klionsky,et al.  Atg11 links cargo to the vesicle-forming machinery in the cytoplasm to vacuole targeting pathway. , 2005, Molecular biology of the cell.

[17]  Chao Zhang,et al.  Chemical genetic analysis of Apg1 reveals a non-kinase role in the induction of autophagy. , 2003, Molecular biology of the cell.

[18]  D. Klionsky,et al.  Mechanism of cargo selection in the cytoplasm to vacuole targeting pathway. , 2002, Developmental cell.

[19]  Takeshi Noda,et al.  Apg2p Functions in Autophagosome Formation on the Perivacuolar Structure* , 2001, The Journal of Biological Chemistry.

[20]  D. Klionsky,et al.  Cvt19 is a receptor for the cytoplasm-to-vacuole targeting pathway. , 2001, Molecular cell.

[21]  D. Klionsky,et al.  Cvt9/Gsa9 Functions in Sequestering Selective Cytosolic Cargo Destined for the Vacuole , 2001, The Journal of cell biology.

[22]  Kazuya Nagano,et al.  Tor-Mediated Induction of Autophagy via an Apg1 Protein Kinase Complex , 2000, The Journal of cell biology.

[23]  A. Matsuura,et al.  Apg1p, a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae. , 1997, Gene.