Exit from the Golgi is required for the expansion of the autophagosomal phagophore in yeast Saccharomyces cerevisiae.
The delivery of proteins and organelles to the vacuole by autophagy involves membrane rearrangements that result in the formation of large vesicles called autophagosomes. The mechanism underlying autophagosome biogenesis and the origin of the membranes composing these vesicles remains largely unclear. We have investigated the role of the Golgi complex in autophagy and have determined that in yeast, activation of ADP-ribosylation factor (Arf)1 and Arf2 GTPases by Sec7, Gea1, and Gea2 is essential for this catabolic process. The two main events catalyzed by these components, the biogenesis of COPI- and clathrin-coated vesicles, do not play a critical role in autophagy. Analysis of the sec7 strain under starvation conditions revealed that the autophagy machinery is correctly assembled and the precursor membrane cisterna of autophagosomes, the phagophore, is normally formed. However, the expansion of the phagophore into an autophagosome is severely impaired. Our data show that the Golgi complex plays a crucial role in supplying the lipid bilayers necessary for the biogenesis of double-membrane vesicles possibly through a new class of transport carriers or a new mechanism.
van der Vaart
Aniek
A
Department of Cell Biology and Institute of Biomembranes, University Medical Center Utrecht, Utrecht 3584, The Netherlands.
Griffith
Janice
J
Reggiori
Fulvio
F
D020823:ADP-Ribosylation Factor 1 / Q000235:genetics / Q000378:metabolism; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism; D000935:Antifungal Agents / Q000494:pharmacology; D001343:Autophagy / Q000502:physiology*; D000071190:Autophagy-Related Protein 8 Family; D006056:Golgi Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism* / Q000648:ultrastructure; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism* / Q000648:ultrastructure*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D020123:Sirolimus / Q000494:pharmacology; D014617:Vacuoles / Q000378:metabolism
C113757:ATG8 protein, S cerevisiae; D000935:Antifungal Agents; D000071190:Autophagy-Related Protein 8 Family; C102475:GEA1 protein, S cerevisiae; C121632:GEA2 protein, S cerevisiae; D020662:Guanine Nucleotide Exchange Factors; D008869:Microtubule-Associated Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C066755:Sec7 guanine nucleotide exchange factors; C116686:ARF2 protein, S cerevisiae; D020823:ADP-Ribosylation Factor 1; D020727:ADP-Ribosylation Factors; D020123:Sirolimus
J Cell Biol. 1999 Oct 18;147(2):435-46
10525546
J Biol Chem. 2002 Jan 4;277(1):763-73
11675395
Biochim Biophys Acta. 2009 Sep;1793(9):1404-12
19264099
J Biol Chem. 2001 Aug 10;276(32):30452-60
11382761
EMBO J. 2001 Nov 1;20(21):5971-81
11689437
J Biol Chem. 2003 Feb 14;278(7):5009-20
12446664
Mol Biol Cell. 2004 Aug;15(8):3553-66
15155809
Dev Cell. 2008 Sep;15(3):344-357
18804433
Mol Cell Biol. 1988 Nov;8(11):4936-48
3062374
Traffic. 2007 Nov;8(11):1476-85
17850229
Dev Cell. 2004 Jan;6(1):79-90
14723849
Traffic. 2008 Jul;9(7):1060-72
18429928
Yeast. 1998 Jul;14(10):953-61
9717241
Cell Death Differ. 2009 Jan;16(1):94-102
19079287
J Cell Sci. 2001 Jun;114(Pt 12):2241-53
11493664
J Biol Chem. 2004 Jul 16;279(29):29889-94
15138258
EMBO J. 1993 Mar;12(3):869-77
8458343
J Cell Biol. 1997 Dec 29;139(7):1687-95
9412464
J Histochem Cytochem. 1990 Apr;38(4):573-80
2319125
J Biol Chem. 2008 Aug 29;283(35):23972-80
18586673
Mol Biol Cell. 2000 Aug;11(8):2673-89
10930462
EMBO J. 2000 Apr 3;19(7):1494-504
10747018
Nature. 2006 Jun 22;441(7096):1002-6
16699524
Genes Cells. 2007 Feb;12(2):209-18
17295840
J Cell Biol. 1997 Aug 11;138(3):517-29
9245783
Annu Rev Cell Dev Biol. 2007;23:579-611
17506703
EMBO Rep. 2008 Sep;9(9):859-64
18704115
Nature. 2009 Oct 1;461(7264):654-8
19794493
J Biol Chem. 1998 Jun 19;273(25):15818-29
9624182
J Cell Sci. 2006 Jul 15;119(Pt 14):2903-11
16787937
J Cell Biol. 2006 Dec 18;175(6):925-35
17178909
Cell Mol Life Sci. 2008 Nov;65(21):3433-45
18604628
Curr Top Dev Biol. 2006;74:1-30
16860663
Cell. 1980 Aug;21(1):205-15
6996832
Mol Biol Cell. 2003 Jun;14(6):2357-71
12808035
Mol Biol Cell. 2008 Nov;19(11):4762-75
18768753
Autophagy. 2008 Feb;4(2):151-75
18188003
Biochem Biophys Res Commun. 1995 May 5;210(1):126-32
7741731
Nature. 2008 Feb 28;451(7182):1069-75
18305538
Curr Opin Cell Biol. 2003 Aug;15(4):396-404
12892779
J Membr Biol. 2006;211(2):65-79
17041781
Mol Cell Biol. 1996 Jul;16(7):3275-84
8668142
Mol Biol Cell. 2010 Jul 1;21(13):2257-69
20444978
J Cell Biol. 2000 Feb 7;148(3):465-80
10662773
Nat Rev Mol Cell Biol. 2008 Apr;9(4):273-84
18354421
Cell. 1998 Feb 6;92(3):415-23
9476900
EMBO J. 1996 Apr 15;15(8):1792-8
8617224
J Biol Chem. 2005 Oct 14;280(41):34489-99
16100119
EMBO J. 1989 Sep;8(9):2695-702
2684655
Mol Biol Cell. 2005 Jul;16(7):3438-53
15901835
Mol Biol Cell. 2005 Dec;16(12):5843-56
16221887
Traffic. 2008 May;9(5):755-69
18298591
Mol Biol Cell. 2004 May;15(5):2189-204
15004240
J Biol Chem. 2008 Jun 13;283(24):16915-27
18397879
J Cell Biol. 1992 Oct;119(2):301-11
1400575
Microbiology (Reading). 2001 Sep;147(Pt 9):2409-2415
11535781
Mol Biol Cell. 2008 May;19(5):1962-75
18287533
Mol Cell. 1999 Mar;3(3):275-85
10198630
Nat Cell Biol. 2007 Oct;9(10):1102-9
17909521
Traffic. 2008 Mar;9(3):281-9
17988219
Nat Rev Immunol. 2008 Aug;8(8):607-18
18641646
J Cell Biol. 2009 Apr 20;185(2):305-21
19364919
J Cell Biol. 2001 Feb 19;152(4):657-68
11266458
Traffic. 2008 Apr;9(4):559-73
18208507
Mol Biol Cell. 1998 Mar;9(3):653-70
9487133
Trends Cell Biol. 2000 Feb;10(2):60-7
10652516
Autophagy. 2005 Jul;1(2):101-9
16874040
Genetics. 1999 Aug;152(4):1543-56
10430582
Dev Cell. 2002 Dec;3(6):825-37
12479808