title: Linkage of autophagy to fungal development, lipid storage and virulence in Metarhizium robertsii.
abstract: Autophagy is a highly conserved process that maintains intracellular homeostasis by degrading proteins or organelles in all eukaryotes. The effect of autophagy on fungal biology and infection of insect pathogens is unknown. Here, we report the function of MrATG8, an ortholog of yeast ATG8, in the entomopathogenic fungus Metarhizium robertsii. MrATG8 can complement an ATG8-defective yeast strain and deletion of MrATG8 impaired autophagy, conidiation and fungal infection biology in M. robertsii. Compared with the wild-type and gene-rescued mutant, Mratg8Δ is not inductive to form the infection-structure appressorium and is impaired in defense response against insect immunity. In addition, accumulation of lipid droplets (LDs) is significantly reduced in the conidia of Mratg8Δ and the pathogenicity of the mutant is drastically impaired. We also found that the cellular level of a LD-specific perilipin-like protein is significantly lowered by deletion of MrATG8 and that the carboxyl terminus beyond the predicted protease cleavage site is dispensable for MrAtg8 function. To corroborate the role of autophagy in fungal physiology, the homologous genes of yeast ATG1, ATG4 and ATG15, designated as MrATG1, MrATG4 and MrATG15, were also deleted in M. robertsii. In contrast to Mratg8Δ, these mutants could form appressoria, however, the LD accumulation and virulence were also considerably impaired in the mutant strains. Our data showed that autophagy is required in M. robertsii for fungal differentiation, lipid biogenesis and insect infection. The results advance our understanding of autophagic process in fungi and provide evidence to connect autophagy with lipid metabolism.
authors: Key Laboratory of Insect Developmental and Evolutionary Biology, Institute of Plant Physiology and Ecology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors: Zhibing
authors: Z
authors: Duan
authors: Yixiong
authors: Y
authors: Chen
authors: Wei
authors: W
authors: Huang
authors: Yanfang
authors: Y
authors: Shang
authors: Peilin
authors: P
authors: Chen
authors: Chengshu
authors: C
authors: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001343:Autophagy / Q000235:genetics; D012831:Bombyx / Q000382:microbiology; D019143:Evolution, Molecular; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000235:genetics; D005998:Glycine / Q000378:metabolism; D050356:Lipid Metabolism; D052981:Metarhizium / Q000166:cytology / Q000235:genetics / Q000254:growth & development* / Q000472:pathogenicity*; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000235:genetics; D010641:Phenotype; D013172:Spores, Fungal / Q000166:cytology / Q000254:growth & development / Q000648:ultrastructure; D014158:Transcription, Genetic; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D005998:Glycine
keywords: Metarhizium robertsii; appressorium; autophagy; cell differentiation; lipid metabolism; perilipin; sporulation; virulence
references: Biochim Biophys Acta. 2009 Jun;1791(6):419-40
references: 19375517
references: Autophagy. 2012 Mar;8(3):326-37
references: 22240663
references: Fungal Genet Biol. 2011 Mar;48(3):217-24
references: 21094265
references: Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1287-92
references: 22232661
references: Annu Rev Immunol. 2012;30:611-46
references: 22449030
references: J Clin Invest. 2009 Nov;119(11):3329-39
references: 19855132
references: Autophagy. 2007 May-Jun;3(3):181-206
references: 17224625
references: Eukaryot Cell. 2007 Jun;6(6):997-1005
references: 17416896
references: Fungal Genet Biol. 2009 Jan;46(1):1-8
references: 19010432
references: EMBO J. 2001 Nov 1;20(21):5971-81
references: 11689437
references: PLoS Genet. 2011 Jan 06;7(1):e1001264
references: 21253567
references: Autophagy. 2010 Jan;6(1):74-85
references: 19923912
references: Autophagy. 2009 Oct;5(7):1041-2
references: 19597345
references: Nat Rev Mol Cell Biol. 2007 Nov;8(11):931-7
references: 17712358
references: J Cell Biol. 1999 Oct 18;147(2):435-46
references: 10525546
references: Genome Biol. 2011 Jul 27;12(7):226
references: 21867568
references: Science. 2006 Apr 28;312(5773):580-3
references: 16645096
references: Eukaryot Cell. 2005 May;4(5):937-47
references: 15879528
references: PLoS Pathog. 2012;8(5):e1002695
references: 22615560
references: Autophagy. 2011 May;7(5):525-30
references: 21317549
references: Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15967-72
references: 19717456
references: Nat Rev Mol Cell Biol. 2011 Jan;12(1):9-14
references: 21179058
references: Trends Endocrinol Metab. 2011 Jun;22(6):234-40
references: 21419642
references: Proc Natl Acad Sci U S A. 2006 Apr 25;103(17):6647-52
references: 16614065
references: Appl Microbiol Biotechnol. 2010 Jan;85(4):901-7
references: 19862514
references: J Biol Chem. 2007 Jul 20;282(29):21110-5
references: 17526497
references: Mol Plant Pathol. 2010 Jul;11(4):463-78
references: 20618705
references: FEMS Microbiol Lett. 2011 Mar;316(1):61-9
references: 21204928
references: Biochim Biophys Acta. 2012 Jan;1824(1):44-50
references: 21640203
references: Sci Rep. 2012;2:483
references: 22761991
references: Autophagy. 2008 Nov;4(8):982-8
references: 18927489
references: Int J Cell Biol. 2011;2011:713435
references: 22013444
references: Autophagy. 2009 Oct;5(7):946-53
references: 19556868
references: Environ Microbiol. 2009 Sep;11(9):2351-60
references: 19538505
references: Nature. 2009 Apr 30;458(7242):1131-5
references: 19339967
references: J Biol Chem. 2004 Nov 12;279(46):47704-10
references: 15355958
references: FEBS Lett. 2010 Apr 2;584(7):1350-8
references: 20079356
references: Biochim Biophys Acta. 2009 Jun;1791(6):408-18
references: 19118639
references: Eukaryot Cell. 2006 Aug;5(8):1328-36
references: 16896216
references: Antioxid Redox Signal. 2011 May 15;14(10):1989-2001
references: 21194379
references: Autophagy. 2008 Oct;4(7):874-86
references: 18690010
references: PLoS Pathog. 2012 Feb;8(2):e1002514
references: 22346750
references: Autophagy. 2012 Jul 1;8(7):1159-62
references: 22722653
references: FEBS Lett. 2010 Apr 2;584(7):1367-73
references: 20083110
references: Nat Cell Biol. 2007 Oct;9(10):1102-9
references: 17909521