Multiple mitochondrial thioesterases have distinct tissue and substrate specificity and CoA regulation, suggesting unique functional roles.
acyl-CoA thioesterase (Acot)
allosteric regulation
coenzyme A (CoA)
enzyme compartmentalization
fatty acid oxidation
lipid hydrolase
lipid metabolism
long-chain acyl-CoA regulation
mitochondria
mitochondrial matrix
mitochondrial metabolism
mouse
subcellular localization
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
13 12 2019
13 12 2019
Historique:
received:
03
09
2019
revised:
16
10
2019
pubmed:
5
11
2019
medline:
14
7
2020
entrez:
3
11
2019
Statut:
ppublish
Résumé
Acyl-CoA thioesterases (Acots) hydrolyze fatty acyl-CoA esters. Acots in the mitochondrial matrix are poised to mitigate β-oxidation overload and maintain CoA availability. Several Acots associate with mitochondria, but whether they all localize to the matrix, are redundant, or have different roles is unresolved. Here, we compared the suborganellar localization, activity, expression, and regulation among mitochondrial Acots (Acot2, -7, -9, and -13) in mitochondria from multiple mouse tissues and from a model of Acot2 depletion. Acot7, -9, and -13 localized to the matrix, joining Acot2 that was previously shown to localize there. Mitochondria from heart, skeletal muscle, brown adipose tissue, and kidney robustly expressed Acot2, -9, and -13; Acot9 levels were substantially higher in brown adipose tissue and kidney mitochondria, as was activity for C4:0-CoA, a unique Acot9 substrate. In all tissues, Acot2 accounted for about half of the thioesterase activity for C14:0-CoA and C16:0-CoA. In contrast, liver mitochondria from fed and fasted mice expressed little Acot activity, which was confined to long-chain CoAs and due mainly to Acot7 and Acot13 activities. Matrix Acots occupied different functional niches, based on substrate specificity (Acot9
Identifiants
pubmed: 31676684
pii: S0021-9258(20)30819-X
doi: 10.1074/jbc.RA119.010901
pmc: PMC6916504
doi:
Substances chimiques
Acyl Coenzyme A
0
Recombinant Proteins
0
Acot13 protein, mouse
EC 3.1.2.-
Thiolester Hydrolases
EC 3.1.2.-
Acot7 protein, mouse
EC 3.1.2.2
Palmitoyl-CoA Hydrolase
EC 3.1.2.2
mitochondrial acyl-CoA thioesterase I, mouse
EC 3.1.2.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
19034-19047Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK109100
Pays : United States
Informations de copyright
© 2019 Bekeova et al.
Références
Mol Cell Biol. 2012 Jul;32(14):2685-97
pubmed: 22586271
Trends Endocrinol Metab. 2017 Jul;28(7):473-484
pubmed: 28385385
J Biol Chem. 2007 Oct 19;282(42):30728-36
pubmed: 17704541
J Biol Chem. 1995 May 19;270(20):12177-83
pubmed: 7744868
J Biol Chem. 2010 Sep 24;285(39):29834-41
pubmed: 20663895
Biochem Biophys Res Commun. 2011 Jan 7;404(1):74-8
pubmed: 21094633
Exp Biol Med (Maywood). 2001 Feb;226(2):78-84
pubmed: 11446442
Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6601-6
pubmed: 23576753
Mol Cell Biol. 2013 May;33(9):1869-82
pubmed: 23459938
J Biol Chem. 2008 Sep 12;283(37):25124-31
pubmed: 18628202
PLoS One. 2015 Mar 11;10(3):e0116587
pubmed: 25760036
Biol Pharm Bull. 2011;34(1):87-91
pubmed: 21212523
Hepatology. 2001 May;33(5):1194-205
pubmed: 11343249
Mol Med. 2018 Mar 15;24(1):3
pubmed: 30134787
Cell Rep. 2017 Jun 27;19(13):2836-2852
pubmed: 28658629
Mol Cell Biol. 2012 Feb;32(4):740-50
pubmed: 22158969
Prog Lipid Res. 2002 May;41(3):197-239
pubmed: 11814524
J Lipid Res. 2007 Jul;48(7):1511-7
pubmed: 17438340
J Biol Chem. 1999 Nov 26;274(48):34317-26
pubmed: 10567408
Biochem Biophys Res Commun. 2009 Aug 7;385(4):630-3
pubmed: 19497300
J Biol Chem. 2002 Feb 1;277(5):3424-32
pubmed: 11694534
Biochem J. 2009 Jun 26;421(2):311-22
pubmed: 19405909
FASEB J. 2012 May;26(5):2209-21
pubmed: 22345407
FASEB J. 2006 Sep;20(11):1855-64
pubmed: 16940157
Cell Mol Life Sci. 2014 Mar;71(5):933-48
pubmed: 23864032
Circ Res. 2013 Dec 6;113(12):1308-19
pubmed: 24062335
Cardiovasc Res. 2015 Jul 15;107(2):235-45
pubmed: 26023060
Diabetes. 2017 Aug;66(8):2112-2123
pubmed: 28607105
J Biol Chem. 1985 Jan 25;260(2):1311-25
pubmed: 3968063
J Biochem. 1999 Dec;126(6):1013-9
pubmed: 10578051
J Biol Chem. 2002 Jan 11;277(2):1128-38
pubmed: 11673457
FASEB J. 2003 Jun;17(9):1112-4
pubmed: 12692085
FEBS Lett. 2002 Aug 14;525(1-3):7-12
pubmed: 12163152
Nucleic Acids Res. 2016 Jan 4;44(D1):D1251-7
pubmed: 26450961
J Lipid Res. 2014 Dec;55(12):2458-70
pubmed: 25114170
J Lipid Res. 2000 May;41(5):814-23
pubmed: 10787442
J Clin Invest. 2018 Jan 2;128(1):141-156
pubmed: 29202465
Am J Physiol Endocrinol Metab. 2004 Nov;287(5):E888-95
pubmed: 15292030
Biochem J. 1998 Feb 1;329 ( Pt 3):601-8
pubmed: 9445388
Exp Cell Res. 2002 Mar 10;274(1):100-11
pubmed: 11855861
Mol Cell. 2013 Jan 10;49(1):186-99
pubmed: 23201123
Biochemistry. 2012 Sep 4;51(35):6990-9
pubmed: 22897136
J Biol Chem. 2019 Feb 8;294(6):2009-2020
pubmed: 30523156
Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10382-7
pubmed: 17563367
PLoS Comput Biol. 2017 Apr 3;13(4):e1005461
pubmed: 28369071
J Cell Biol. 2018 Apr 2;217(4):1369-1382
pubmed: 29382700
Am J Physiol Cell Physiol. 2006 Dec;291(6):C1198-207
pubmed: 16855217
J Lipid Res. 2012 Dec;53(12):2620-31
pubmed: 22993230
PLoS Comput Biol. 2013;9(8):e1003186
pubmed: 23966849