title: Glucose starvation inhibits autophagy via vacuolar hydrolysis and induces plasma membrane internalization by down-regulating recycling.
abstract: Cellular energy influences all aspects of cellular function. Although cells can adapt to a gradual reduction in energy, acute energy depletion poses a unique challenge. Because acute depletion hampers the transport of new energy sources into the cell, the cell must use endogenous substrates to replenish energy after acute depletion. In the yeast Saccharomyces cerevisiae, glucose starvation causes an acute depletion of intracellular energy that recovers during continued glucose starvation. However, how the cell replenishes energy during the early phase of glucose starvation is unknown. In this study, we investigated the role of pathways that deliver proteins and lipids to the vacuole during glucose starvation. We report that in response to glucose starvation, plasma membrane proteins are directed to the vacuole through reduced recycling at the endosomes. Furthermore, we found that vacuolar hydrolysis inhibits macroautophagy in a target of rapamycin complex 1-dependent manner. Accordingly, we found that endocytosis and hydrolysis are required for survival in glucose starvation, whereas macroautophagy is dispensable. Together, these results suggest that hydrolysis of components delivered to the vacuole independent of autophagy is the cell survival mechanism used by S. cerevisiae in response to glucose starvation.
authors.affiliation: From the Department of Cell and Developmental Biology, the University of Michigan, Ann Arbor, Michigan 48109.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lang
authors.affiliation: From the Department of Cell and Developmental Biology, the University of Michigan, Ann Arbor, Michigan 48109.
authors.forename: Jorge Y
authors.initials: JY
authors.lastname: Martinez-Marquez
authors.affiliation: the Department of Biology, the Johns Hopkins University, Baltimore, Maryland 21218, and.
authors.forename: Derek C
authors.initials: DC
authors.lastname: Prosser
authors.affiliation: the Department of Biology, the University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: Laura R
authors.initials: LR
authors.lastname: Ganser
authors.affiliation: the Curriculum in Genetics and Molecular Biology, the University of North Carolina, Chapel Hill, North Carolina 27599.
authors.forename: Destiney
authors.initials: D
authors.lastname: Buelto
authors.affiliation: the Department of Biology, the Johns Hopkins University, Baltimore, Maryland 21218, and.
authors.forename: Beverly
authors.initials: B
authors.lastname: Wendland
authors.affiliation: From the Department of Cell and Developmental Biology, the University of Michigan, Ann Arbor, Michigan 48109, the Department of Biology, the University of North Carolina, Chapel Hill, North Carolina 27599, the Curriculum in Genetics and Molecular Biology, the University of North Carolina, Chapel Hill, North Carolina 27599 mcduncan@umich.edu.
authors.forename: Mara C
authors.initials: MC
authors.lastname: Duncan
mesh_terms: D001343:Autophagy; D002462:Cell Membrane / Q000378:metabolism*; D015536:Down-Regulation; D004705:Endocytosis; D005947:Glucose / Q000172:deficiency* / Q000378:metabolism; D006868:Hydrolysis; D050356:Lipid Metabolism; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes / Q000378:metabolism; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D005947:Glucose
keywords: Autophagy; Endocytosis; Endosome; Energy Metabolism; Glucose; Intracellular Trafficking; Lysosome; Membrane Recycling
references.citation: J Cell Biol. 1999 Oct 18;147(2):435-46
references.pmid: 10525546
references.citation: Yeast. 1995 Jan;11(1):53-5
references.pmid: 7762301
references.citation: Cell. 2001 Apr 6;105(1):93-102
references.pmid: 11301005
references.citation: Mol Biol Cell. 2007 Oct;18(10):4180-9
references.pmid: 17699586
references.citation: Nat Cell Biol. 2012 Feb 19;14(3):239-48
references.pmid: 22344030
references.citation: Yeast. 2001 Jan 15;18(1):1-18
references.pmid: 11124697
references.citation: Cell Metab. 2011 May 4;13(5):495-504
references.pmid: 21531332
references.citation: Methods Enzymol. 2008;451:33-42
references.pmid: 19185711
references.citation: Traffic. 2012 Mar;13(3):468-82
references.pmid: 22118530
references.citation: J Biol Chem. 2013 Dec 13;288(50):35769-80
references.pmid: 24174532
references.citation: Autophagy. 2006 Apr-Jun;2(2):146-8
references.pmid: 16874100
references.citation: J Biol Chem. 1994 May 13;269(19):14064-74
references.pmid: 7514599
references.citation: Mol Biol Cell. 2011 Oct;22(19):3671-83
references.pmid: 21832155
references.citation: J Biol Chem. 1994 Apr 1;269(13):9833-41
references.pmid: 8144575
references.citation: Traffic. 2007 Nov;8(11):1554-67
references.pmid: 17908202
references.citation: Mol Biol Cell. 2000 Mar;11(3):833-48
references.pmid: 10712503
references.citation: J Cell Biol. 2000 Sep 18;150(6):1507-13
references.pmid: 10995454
references.citation: Mol Biol Cell. 1998 Jun;9(6):1323-37
references.pmid: 9614177
references.citation: EMBO J. 2010 Aug 4;29(15):2515-26
references.pmid: 20581803
references.citation: Mol Pharmacol. 1993 Aug;44(2):364-70
references.pmid: 8394993
references.citation: Mol Biol Cell. 2007 Jan;18(1):295-312
references.pmid: 17093059
references.citation: Mol Cell Biol. 1986 Jul;6(7):2500-10
references.pmid: 3537721
references.citation: Biochem Soc Trans. 2011 Apr;39(2):437-42
references.pmid: 21428915
references.citation: J Cell Biol. 1998 Sep 7;142(5):1289-99
references.pmid: 9732289
references.citation: Mol Biol Cell. 2004 Apr;15(4):1544-56
references.pmid: 14742701
references.citation: Yeast. 1998 Jul;14(10):953-61
references.pmid: 9717241
references.citation: Curr Biol. 2013 May 6;23(9):770-4
references.pmid: 23623551
references.citation: Genes Dev. 2011 Feb 15;25(4):336-49
references.pmid: 21289062
references.citation: J Exp Biol. 2002 May;205(Pt 9):1209-19
references.pmid: 11948198
references.citation: J Cell Biol. 2011 Nov 14;195(4):657-71
references.pmid: 22065638
references.citation: J Pathol. 2010 Jun;221(2):117-24
references.pmid: 20225337
references.citation: Mol Biol Cell. 2008 Aug;19(8):3526-35
references.pmid: 18508916
references.citation: J Exp Biol. 1992 Nov;172:105-12
references.pmid: 1491220
references.citation: J Biol Chem. 1985 Jan 10;260(1):128-33
references.pmid: 3965443
references.citation: Proc Natl Acad Sci U S A. 2006 Dec 19;103(51):19302-7
references.pmid: 17159141
references.citation: Mol Biol Cell. 2002 Oct;13(10):3672-82
references.pmid: 12388765
references.citation: Science. 2011 Nov 4;334(6056):678-83
references.pmid: 22053050
references.citation: Mol Cell Biol. 1986 Jul;6(7):2490-9
references.pmid: 3023936
references.citation: Mol Cell. 2012 Apr 13;46(1):105-10
references.pmid: 22424774
references.citation: EMBO J. 1997 Apr 15;16(8):1820-31
references.pmid: 9155008
references.citation: Mol Cell Proteomics. 2002 Mar;1(3):232-42
references.pmid: 12096123
references.citation: Autophagy. 2012 Apr;8(4):445-544
references.pmid: 22966490
references.citation: J Cell Biol. 1999 Sep 20;146(6):1227-38
references.pmid: 10491387
references.citation: Science. 2009 May 22;324(5930):1029-33
references.pmid: 19460998
references.citation: Mol Biol Cell. 2008 May;19(5):1991-2002
references.pmid: 18287542
references.citation: Autophagy. 2011 Oct;7(10):1093-4
references.pmid: 21993240
references.citation: Mol Biol Cell. 2013 Mar;24(6):832-47
references.pmid: 23345590
references.citation: Science. 2008 Jun 13;320(5882):1496-501
references.pmid: 18497260
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17049-54
references.pmid: 19805182
references.citation: EMBO J. 1990 Nov;9(11):3477-87
references.pmid: 2209555
references.citation: J Biol Chem. 2001 Dec 14;276(50):47411-20
references.pmid: 11592965
references.citation: Mol Biol Cell. 2005 Jan;16(1):178-92
references.pmid: 15537705
references.citation: Mol Biol Cell. 2008 Jul;19(7):2936-48
references.pmid: 18448668
references.citation: Mol Microbiol. 1999 Sep;33(5):904-18
references.pmid: 10476026
references.citation: J Cell Biol. 1992 Oct;119(2):301-11
references.pmid: 1400575
references.citation: Mol Cell Biol. 2007 Jan;27(2):605-21
references.pmid: 17101785
references.citation: J Biol Chem. 2001 Jan 19;276(3):2083-7
references.pmid: 11085977
references.citation: Traffic. 2010 Sep;11(9):1141-50
references.pmid: 20626707
references.citation: EMBO J. 2001 Nov 1;20(21):5971-81
references.pmid: 11689437
references.citation: Autophagy. 2012 Dec;8(12):1875-6
references.pmid: 22874642
references.citation: Cell. 1986 Dec 26;47(6):1041-51
references.pmid: 3536126
references.citation: J Cell Biol. 2000 Apr 17;149(2):397-410
references.pmid: 10769031
references.citation: Cell Death Differ. 2013 Jan;20(1):43-8
references.pmid: 22705847
references.citation: J Gen Microbiol. 1968 May;51(3):447-55
references.pmid: 5657265
references.citation: Cell Metab. 2011 Nov 2;14(5):707-14
references.pmid: 22019086
references.citation: Gene. 1996 Oct 31;178(1-2):139-43
references.pmid: 8921905
references.citation: Nat Cell Biol. 1999 Aug;1(4):234-41
references.pmid: 10559922