Mitochondrial contact site and cristae organizing system (MICOS) machinery supports heme biosynthesis by enabling optimal performance of ferrochelatase.
Ferrochelatase
Heme
MICOS
Mitochondria
Yeast
Journal
Redox biology
ISSN: 2213-2317
Titre abrégé: Redox Biol
Pays: Netherlands
ID NLM: 101605639
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
12
07
2021
revised:
31
08
2021
accepted:
03
09
2021
pubmed:
14
9
2021
medline:
26
10
2021
entrez:
13
9
2021
Statut:
ppublish
Résumé
Heme is an essential cofactor required for a plethora of cellular processes in eukaryotes. In metazoans the heme biosynthetic pathway is typically partitioned between the cytosol and mitochondria, with the first and final steps taking place in the mitochondrion. The pathway has been extensively studied and its biosynthetic enzymes structurally characterized to varying extents. Nevertheless, understanding of the regulation of heme synthesis and factors that influence this process in metazoans remains incomplete. Therefore, we investigated the molecular organization as well as the physical and genetic interactions of the terminal pathway enzyme, ferrochelatase (Hem15), in the yeast Saccharomyces cerevisiae. Biochemical and genetic analyses revealed dynamic association of Hem15 with Mic60, a core component of the mitochondrial contact site and cristae organizing system (MICOS). Loss of MICOS negatively impacts Hem15 activity, affects the size of the Hem15 high-mass complex, and results in accumulation of reactive and potentially toxic tetrapyrrole precursors that may cause oxidative damage. Restoring intermembrane connectivity in MICOS-deficient cells mitigates these cytotoxic effects. These data provide new insights into how heme biosynthetic machinery is organized and regulated, linking mitochondrial architecture-organizing factors to heme homeostasis.
Identifiants
pubmed: 34517185
pii: S2213-2317(21)00284-6
doi: 10.1016/j.redox.2021.102125
pmc: PMC8441213
pii:
doi:
Substances chimiques
Mitochondrial Proteins
0
Heme
42VZT0U6YR
Ferrochelatase
EC 4.99.1.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
102125Subventions
Organisme : NIGMS NIH HHS
ID : R35 GM131701
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM108975
Pays : United States
Organisme : NIEHS NIH HHS
ID : R33 ES025661
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM107001
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM089778
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.
Références
Biochemistry. 2007 Jul 10;46(27):7973-9
pubmed: 17567154
Pediatr Pulmonol. 1989;7(4):209-16
pubmed: 2694087
J Bacteriol. 1993 Apr;175(7):2154-6
pubmed: 8458858
Elife. 2017 May 29;6:
pubmed: 28553927
J Biol Chem. 2010 Jun 18;285(25):19450-9
pubmed: 20404342
J Cell Biol. 2019 Apr 1;218(4):1353-1369
pubmed: 30674579
Biochemistry. 1985 Jan 15;24(2):366-70
pubmed: 3884041
J Mol Biol. 1991 Jun 5;219(3):393-8
pubmed: 2051480
Science. 2013 Mar 15;339(6125):1328-1331
pubmed: 23371551
Curr Opin Chem Biol. 2013 Apr;17(2):204-11
pubmed: 23415705
Acc Chem Res. 2016 Jun 21;49(6):1104-10
pubmed: 27254265
Dev Cell. 2011 Oct 18;21(4):694-707
pubmed: 21944719
Nat Protoc. 2007;2(11):2728-33
pubmed: 18007608
iScience. 2021 Jan 29;24(2):102119
pubmed: 33644718
Biotechniques. 2016 Aug 01;61(2):83-91
pubmed: 27528073
J Biol Chem. 1990 May 5;265(13):7278-83
pubmed: 2185242
Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4672-6
pubmed: 10758168
J Pharmacol Exp Ther. 2016 Feb;356(2):267-75
pubmed: 26588930
Chem Rev. 2014 Apr 9;114(7):3919-62
pubmed: 24400737
Biochemistry. 2007 Jul 10;46(27):8121-7
pubmed: 17566985
Elife. 2015 Apr 28;4:
pubmed: 25918844
Mol Gen Genet. 1995 Nov 1;249(1):1-7
pubmed: 8552025
Biochim Biophys Acta. 1999 Nov 16;1435(1-2):191-7
pubmed: 10561552
Biochem J. 1978 May 15;172(2):345-7
pubmed: 666752
Nature. 2012 Nov 22;491(7425):608-12
pubmed: 23135403
Blood. 2010 Jul 29;116(4):628-30
pubmed: 20427704
J Cell Biol. 2016 Jun 6;213(5):525-34
pubmed: 27241913
Biochemistry. 2012 Jul 10;51(27):5422-33
pubmed: 22712763
Cell Metab. 2018 Mar 6;27(3):645-656.e7
pubmed: 29514071
G3 (Bethesda). 2017 Sep 7;7(9):3083-3090
pubmed: 28717049
Blood. 2018 Sep 6;132(10):987-998
pubmed: 29991557
Biochemistry. 2017 Apr 4;56(13):1815-1823
pubmed: 28316240
Nature. 2008 Oct 30;455(7217):1251-4
pubmed: 18820680
Cold Spring Harb Perspect Med. 2013 Apr 01;3(4):a011676
pubmed: 23471474
Arch Biochem Biophys. 2002 Feb 15;398(2):170-8
pubmed: 11831847
J Biol Chem. 2016 May 6;291(19):10411-25
pubmed: 26940873
Biochemistry. 1996 Dec 17;35(50):16222-9
pubmed: 8973195
Cell Metab. 2012 Dec 5;16(6):801-13
pubmed: 23217259
PLoS One. 2015 Aug 19;10(8):e0135896
pubmed: 26287972
Antioxid Redox Signal. 2016 Feb 20;24(6):281-98
pubmed: 26415097
J Biol Chem. 1986 Feb 25;261(6):2506-9
pubmed: 3512538
Mol Genet Metab. 2019 Nov;128(3):164-177
pubmed: 31326287
J Biol Chem. 1998 Aug 28;273(35):22311-6
pubmed: 9712849
Cell Syst. 2018 Feb 28;6(2):192-205.e3
pubmed: 29361465
Biochim Biophys Acta. 1989 Nov 9;999(1):7-11
pubmed: 2804139
Biochemistry. 2000 Jun 27;39(25):7461-7
pubmed: 10858295
Hum Mol Genet. 2006 Oct 1;15(19):2846-55
pubmed: 16940310
J Biol Chem. 2005 Mar 4;280(9):7645-53
pubmed: 15611069
Biochem Biophys Res Commun. 2003 Oct 31;310(4):1247-53
pubmed: 14559249
Cell Tissue Res. 2017 Jan;367(1):83-93
pubmed: 27245231
Curr Biol. 2015 Jun 1;25(11):1489-95
pubmed: 26004762
Methods Enzymol. 2002;350:3-41
pubmed: 12073320
J Clin Invest. 2014 Oct;124(10):4294-304
pubmed: 25157825
J Biol Chem. 2018 Aug 10;293(32):12378-12393
pubmed: 29921585
Acta Crystallogr D Biol Crystallogr. 2010 Apr;66(Pt 4):486-501
pubmed: 20383002
J Biol Chem. 2011 Feb 4;286(5):3851-62
pubmed: 21115478
J Biol Chem. 2003 Nov 14;278(46):45499-506
pubmed: 12928433
J Cell Sci. 2018 Nov 21;131(22):
pubmed: 30301782
Biochim Biophys Acta. 2016 Jan;1863(1):91-101
pubmed: 26477565
J Biol Chem. 1994 Jan 7;269(1):390-5
pubmed: 8276824
Chem Soc Rev. 2011 Jan;40(1):340-62
pubmed: 20694259
Bioconjug Chem. 2019 May 15;30(5):1297-1303
pubmed: 30986044
J Cell Biol. 2014 Mar 31;204(7):1083-6
pubmed: 24687277
Biochemistry. 2002 Nov 19;41(46):13499-506
pubmed: 12427010
Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):7539-44
pubmed: 27247412
Methods Cell Biol. 2001;65:37-51
pubmed: 11381604
Blood. 2003 Apr 15;101(8):3274-80
pubmed: 12480705
J Biol Chem. 2014 May 9;289(19):13259-72
pubmed: 24648523
Biochem J. 1978 Oct 15;176(1):97-102
pubmed: 31872
Biochem Biophys Res Commun. 1979 Jun 27;88(4):1382-90
pubmed: 289386
Biochim Biophys Acta. 2012 Sep;1823(9):1617-32
pubmed: 22575458
Anal Biochem. 1987 Feb 15;161(1):1-15
pubmed: 3578775
Biochemistry. 2016 Sep 20;55(37):5204-17
pubmed: 27599036
J Biol Chem. 1995 Aug 4;270(31):18198-200
pubmed: 7629135
Biochemistry. 1994 Jan 18;33(2):403-7
pubmed: 8286370
J Cell Sci. 2020 May 20;133(10):
pubmed: 32265272
Eur J Biochem. 1986 May 2;156(3):579-87
pubmed: 3516695
J Biol Chem. 2016 Aug 12;291(33):17417-26
pubmed: 27317660
Mol Cell Biol. 2010 Feb;30(4):1004-17
pubmed: 19995914
J Biol Chem. 2018 Sep 14;293(37):14557-14568
pubmed: 30012884
Haematologica. 2019 Sep;104(9):1756-1767
pubmed: 30765471