Atg32-dependent mitophagy sustains spermidine and nitric oxide required for heat-stress tolerance in Saccharomycescerevisiae.
ATG32
Autophagy
Mitophagy
Nitric oxide
S-adenosyl methionine
Spermidine
Journal
Journal of cell science
ISSN: 1477-9137
Titre abrégé: J Cell Sci
Pays: England
ID NLM: 0052457
Informations de publication
Date de publication:
01 06 2021
01 06 2021
Historique:
received:
07
09
2020
accepted:
06
05
2021
entrez:
7
6
2021
pubmed:
8
6
2021
medline:
13
7
2021
Statut:
ppublish
Résumé
In Saccharomyces cerevisiae, the selective autophagic degradation of mitochondria, termed mitophagy, is critically regulated by the adapter protein Atg32. Despite our knowledge about the molecular mechanisms by which Atg32 controls mitophagy, its physiological roles in yeast survival and fitness remains less clear. Here, we demonstrate a requirement for Atg32 in promoting spermidine production during respiratory growth and heat-induced mitochondrial stress. During respiratory growth, mitophagy-deficient yeast exhibit profound heat-stress induced defects in growth and viability due to impaired biosynthesis of spermidine and its biosynthetic precursor S-adenosyl methionine. Moreover, spermidine production is crucial for the induction of cytoprotective nitric oxide (NO) during heat stress. Hence, the re-addition of spermidine to Atg32 mutant yeast is sufficient to both enhance NO production and restore respiratory growth during heat stress. Our findings uncover a previously unrecognized physiological role for yeast mitophagy in spermidine metabolism and illuminate new interconnections between mitophagy, polyamine biosynthesis and NO signaling.
Identifiants
pubmed: 34096604
pii: 269033
doi: 10.1242/jcs.253781
pmc: PMC8214763
pii:
doi:
Substances chimiques
Autophagy-Related Proteins
0
Receptors, Cytoplasmic and Nuclear
0
Saccharomyces cerevisiae Proteins
0
Nitric Oxide
31C4KY9ESH
Spermidine
U87FK77H25
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : R21 CA201849
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA126792
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA188404
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG057462
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA213775
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA108462
Pays : United States
Organisme : NIDDK NIH HHS
ID : U2C DK119886
Pays : United States
Informations de copyright
© 2021. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests J.D. is a Scientific Advisory Board Member for Vescor Therapeutics, LLC.
Références
J Therm Biol. 2018 Feb;72:73-80
pubmed: 29496018
Mol Biol Cell. 2008 May;19(5):2039-50
pubmed: 18287526
Free Radic Biol Med. 2005 Aug 1;39(3):327-35
pubmed: 15993331
Sci Rep. 2018 Oct 11;8(1):15168
pubmed: 30310096
Cell Death Differ. 2005 Dec;12(12):1613-21
pubmed: 15947785
Biochem Biophys Res Commun. 2013 Jan 4;430(1):137-43
pubmed: 23159617
Mol Genet Genomics. 2006 Aug;276(2):170-86
pubmed: 16741729
Nitric Oxide. 2016 Jul 1;57:85-91
pubmed: 27178802
Biochem J. 2011 Jan 1;433(1):205-13
pubmed: 20942800
Mol Cell. 2011 Jul 8;43(1):19-32
pubmed: 21726807
Eur Heart J. 2012 Apr;33(7):829-37, 837a-837d
pubmed: 21890489
Science. 2018 Jan 26;359(6374):
pubmed: 29371440
J Biol Chem. 2018 Jul 20;293(29):11537-11552
pubmed: 29895621
J Cell Biol. 2016 Dec 19;215(6):779-788
pubmed: 27899413
Neural Regen Res. 2013 Jul 25;8(21):2003-14
pubmed: 25206509
J Cell Biol. 2001 Apr 16;153(2):381-96
pubmed: 11309418
J Biol Chem. 2012 Jan 27;287(5):3265-72
pubmed: 22157017
Nat Cell Biol. 2018 Jul;20(7):745-754
pubmed: 29950572
Yeast. 1998 Jul;14(10):953-61
pubmed: 9717241
Cell Metab. 2019 Aug 6;30(2):352-363.e8
pubmed: 31130465
Sci Rep. 2016 Apr 19;6:24700
pubmed: 27089984
J Biol Chem. 2008 Nov 21;283(47):32386-93
pubmed: 18818209
Cell Death Differ. 2015 Mar;22(3):509-16
pubmed: 25526088
Mol Microbiol. 2010 Feb;75(4):795-800
pubmed: 20487284
J Bacteriol. 1978 Apr;134(1):214-20
pubmed: 348679
Microb Cell. 2015 Mar 02;2(3):91-93
pubmed: 28357282
Biochim Biophys Acta. 1969 Apr 1;177(2):361-4
pubmed: 4888776
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
J Therm Biol. 2018 May;74:256-263
pubmed: 29801636
Nature. 2016 Jan 7;529(7584):37-42
pubmed: 26738589
J Aging Res. 2011 Mar 31;2011:673185
pubmed: 21584246
Food Chem Toxicol. 2014 Sep;71:128-35
pubmed: 24952311
J Cell Biol. 2011 May 16;193(4):755-67
pubmed: 21576396
Curr Genet. 2018 Aug;64(4):907-917
pubmed: 29423676
Nat Cell Biol. 2009 Nov;11(11):1305-14
pubmed: 19801973
Nat Med. 2016 Dec;22(12):1428-1438
pubmed: 27841876
Yeast. 1998 Dec;14(16):1511-27
pubmed: 9885153
Autophagy. 2009 Nov;5(8):1186-9
pubmed: 19806021
BMB Rep. 2017 Jun;50(6):299-307
pubmed: 28366191
Dev Cell. 2009 Jul;17(1):98-109
pubmed: 19619495
J Cell Biol. 2011 Feb 21;192(4):615-29
pubmed: 21339330
Plant Cell Physiol. 2006 Mar;47(3):346-54
pubmed: 16415068
Dev Cell. 2009 Jul;17(1):87-97
pubmed: 19619494