Nutrient-regulated Phosphorylation of ATG13 Inhibits Starvation-induced Autophagy.

The Journal of Biological Chemistry
Cindy PuenteXuejun Jiang

Abstract

Autophagy is a conserved catabolic process that utilizes a defined series of membrane trafficking events to generate a de novo double-membrane vesicle termed the autophagosome, which matures by fusing to the lysosome. Subsequently, the lysosome facilitates the degradation and recycling of the cytoplasmic cargo. In yeast, the upstream signals that regulate the induction of starvation-induced autophagy are clearly defined. The nutrient-sensing kinase Tor inhibits the activation of autophagy by regulating the formation of the Atg1-Atg13-Atg17 complex, through hyperphosphorylation of Atg13. However, in mammals, the ortholog complex ULK1-ATG13-FIP200 is constitutively formed. As such, the molecular mechanism by which mTOR regulates mammalian autophagy is unknown. Here we report the identification and characterization of novel nutrient-regulated phosphorylation sites on ATG13: Ser-224 and Ser-258. mTOR directly phosphorylates ATG13 on Ser-258 while Ser-224 is modulated by the AMPK pathway. In ATG13 knock-out cells reconstituted with an unphosphorylatable mutant of ATG13, ULK1 kinase activity is more potent, and amino acid starvation induced more rapid ATG13 and ULK1 translocation. These events culminated in a more rapid starvation-in...Continue Reading

References

Sep 20, 2000·The Journal of Cell Biology·Y KamadaY Ohsumi
Jun 11, 2002·Methods : a Companion to Methods in Enzymology·G Sebastiaan WinklerPaul Tempst
Mar 4, 2005·Molecular Biology of the Cell·Yukiko KabeyaYoshinori Ohsumi
May 20, 2005·Molecular Biology of the Cell·Heesun CheongDaniel J Klionsky
Feb 14, 2007·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kuninori SuzukiYoshinori Ohsumi
Nov 17, 2007·Genes & Development·Noboru Mizushima
Feb 22, 2008·Molecular Biology of the Cell·Tomoko KawamataYoshinori Ohsumi
Apr 30, 2008·The Journal of Cell Biology·Taichi HaraNoboru Mizushima
Jun 24, 2008·Development·Alicia Meléndez, Thomas P Neufeld
Feb 20, 2009·Molecular Biology of the Cell·Chang Hwa JungDo-Hyung Kim
Mar 5, 2009·The Journal of Biological Chemistry·Ian G GanleyXuejun Jiang
Dec 10, 2009·Molecular and Cellular Biology·Yoshiaki KamadaYoshinori Ohsumi
Sep 3, 2010·Nature Cell Biology·Noboru Mizushima, Beth Levine
Jan 25, 2011·Nature Cell Biology·Joungmok KimKun-Liang Guan
Mar 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Libin ShangXiaodong Wang
Jun 22, 2011·Proceedings of the National Academy of Sciences of the United States of America·Heesun CheongCraig B Thompson
Aug 2, 2011·Annual Review of Cell and Developmental Biology·Noboru MizushimaYoshinori Ohsumi
Aug 23, 2011·Molecular Cell·Joung Hyuck JooMondira Kundu
Dec 25, 2012·Nature Structural & Molecular Biology·Noor GammohXuejun Jiang
Jan 5, 2013·Science·Prashant MaliGeorge M Church
Dec 25, 2013·Cell Research·Yuchen FengDaniel J Klionsky
Dec 25, 2013·Cell Research·Yoshinori Ohsumi
May 6, 2014·Nature Structural & Molecular Biology·Yuko FujiokaNobuo N Noda
Apr 3, 2015·The Journal of Biological Chemistry·Katy J PetherickIan G Ganley
Aug 25, 2015·Molecular Aspects of Medicine·Joohun HaJoungmok Kim
Aug 28, 2015·Nature Communications·Pui-Mun WongXuejun Jiang

❮ Previous
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Citations

Feb 28, 2016·Current Opinion in Cell Biology·Mary G Lin, James H Hurley
Oct 22, 2016·Trends in Biochemical Sciences·Manuela AntonioliGian Maria Fimia
Sep 1, 2017·International Journal of Molecular Sciences·Zhiyuan Li, Xin Zhang
Jan 27, 2018·The Journal of Biological Chemistry·Thomas J MercerSharon A Tooze
Oct 5, 2017·Autophagy·Tamiza NanjiCalvin K Yip
Dec 14, 2017·Essays in Biochemistry·Henri BatokoAgnieszka Sirko
Dec 14, 2017·Essays in Biochemistry·Maria Zachari, Ian G Ganley
Jun 23, 2018·Autophagy·Angel Corona VelazquezWilliam T Jackson
Aug 22, 2018·Molecular and Cellular Biology·Angel F Corona Velazquez, William T Jackson
Aug 23, 2018·The Journal of Biological Chemistry·David ColecchiaMario Chiariello
Oct 3, 2018·European Journal of Immunology·Julie Tellier, Stephen L Nutt
Oct 12, 2018·Traffic·Dudley W Lamming, Liron Bar-Peled
Feb 13, 2019·International Journal of Molecular Sciences·Zhou ZhuMin Li
Oct 5, 2017·Nature Reviews. Molecular Cell Biology·Sébastien Herzig, Reuben J Shaw
Apr 24, 2020·Journal of Integrative Plant Biology·Hua QiShi Xiao
Jun 10, 2020·Archives of Insect Biochemistry and Physiology·Shuyan LiKang Li
Jul 30, 2020·Cell Cycle·Kathryn A JacobsJulie Gavard
Mar 16, 2017·Frontiers in Immunology·Christian W Keller, Jan D Lünemann
Mar 15, 2018·International Journal of Molecular Sciences·Yoana Rabanal-Ruiz, Viktor I Korolchuk
Aug 21, 2019·Frontiers in Oncology·Diane M DemasAyesha N Shajahan-Haq
Jan 11, 2020·Frontiers in Neuroscience·Federica AlbaneseMichele Morari
Mar 27, 2020·Immunological Reviews·Hongling HuangHongbo Chi
Dec 14, 2017·Evidence-based Complementary and Alternative Medicine : ECAM·Yu-Lin ManHong Cheng
Nov 2, 2018·Journal of Cell Science·Satish Babu Moparthi, Thomas Wollert
Nov 9, 2018·Frontiers in Cell and Developmental Biology·Daniel GrassoMaria Ines Vaccaro
Sep 27, 2019·Cancers·Akpedje S Dossou, Alakananda Basu
Jan 16, 2020·Biomolecules·Gur P KaushalSudhir V Shah
May 10, 2020·International Journal of Molecular Sciences·Hyeong Rok YunTae Gyu Choi
Apr 8, 2020·Frontiers in Cell and Developmental Biology·Maria Zachari, Nicholas T Ktistakis
Sep 26, 2020·Cell & Bioscience·Qian SongBosheng Zhao
May 24, 2019·BioMed Research International·Chenlin GaoYong Xu
Aug 7, 2019·International Journal of Molecular Sciences·Gur P KaushalLuis A Juncos
Nov 17, 2019·Apoptosis : an International Journal on Programmed Cell Death·Jennifer MytychMarek Koziorowski
Jul 11, 2018·Development·Lin ShiJen Sheen
May 2, 2020·The Journal of Cell Biology·Thomas J MeliaAnne Simonsen
Nov 22, 2016·The FEBS Journal·Christine R Langlois, Thomas Wollert

❮ Previous
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