Hypoxic Regulation of Mitochondrial Metabolism and Mitophagy in Nucleus Pulposus Cells Is Dependent on HIF-1α-BNIP3 Axis.
BNIP3
HIF-1α
HYPOXIA
INTERVERTEBRAL DISC
METABOLISM
MITOCHONDRIA
MITOPHAGY
MOUSE MODEL
NUCLEUS PULPOSUS
PINK1-PARKIN
Journal
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
ISSN: 1523-4681
Titre abrégé: J Bone Miner Res
Pays: United States
ID NLM: 8610640
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
24
12
2019
revised:
28
02
2020
accepted:
15
03
2020
pubmed:
7
4
2020
medline:
29
7
2021
entrez:
7
4
2020
Statut:
ppublish
Résumé
Nucleus pulposus (NP) cells reside in an avascular and hypoxic microenvironment of the intervertebral disc and are predominantly glycolytic due to robust HIF-1 activity. It is generally thought that NP cells contain few functional mitochondria compared with cells that rely on oxidative metabolism. Consequently, the contribution of mitochondria to NP cell metabolism and the role of hypoxia and HIF-1 in mitochondrial homeostasis is poorly understood. Using mitoQC reporter mice, we show for the first time to our knowledge that NP cell mitochondria undergo age-dependent mitophagy in vivo. Mechanistically, in vitro studies suggest that, under hypoxic conditions, mitochondria in primary NP cells undergo HIF-1α-dependent fragmentation, controlled by modulating the levels of key proteins DRP1 and OPA1 that are involved in mitochondrial fission and fusion, respectively. Seahorse assays and steady state metabolic profiling coupled with [1-2-
Identifiants
pubmed: 32251541
doi: 10.1002/jbmr.4019
pmc: PMC7778522
mid: NIHMS1656878
doi:
Substances chimiques
BNip3 protein, mouse
0
Hypoxia-Inducible Factor 1, alpha Subunit
0
Membrane Proteins
0
Mitochondrial Proteins
0
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
1504-1524Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR064733
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA-56036
Pays : United States
Organisme : NIAMS NIH HHS
ID : T32 AR052273
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01AR064733
Pays : United States
Organisme : NCI NIH HHS
ID : P60DK020541
Pays : United States
Organisme : NIAMS NIH HHS
ID : R03 AR068095
Pays : United States
Organisme : NIDDK NIH HHS
ID : P60 DK020541
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01AR074813
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01AR055655
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR074813
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR055655
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA056036
Pays : United States
Organisme : NIH HHS
ID : R03AR068095
Pays : United States
Informations de copyright
© 2020 American Society for Bone and Mineral Research.
Références
FEBS Lett. 2002 Jul 17;523(1-3):171-6
pubmed: 12123827
PLoS One. 2018 May 16;13(5):e0197266
pubmed: 29768513
Matrix Biol. 2018 Oct;71-72:368-379
pubmed: 29501510
Matrix Biol. 2020 May;87:94-111
pubmed: 31707045
Am J Physiol Gastrointest Liver Physiol. 2009 Mar;296(3):G499-509
pubmed: 19147804
Lancet. 2018 Nov 10;392(10159):1789-1858
pubmed: 30496104
Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12722-7
pubmed: 20616028
Cell Metab. 2006 Mar;3(3):187-97
pubmed: 16517406
Aging Cell. 2018 Oct;17(5):e12800
pubmed: 29963746
Int J Cancer. 2006 Apr 1;118(7):1660-9
pubmed: 16217754
J Biol Chem. 2010 Sep 3;285(36):27879-90
pubmed: 20573959
Mol Biol Cell. 2009 Aug;20(15):3525-32
pubmed: 19477917
Mol Cell Biol. 2012 Jul;32(13):2570-84
pubmed: 22547685
Biology (Basel). 2017 Feb 08;6(1):
pubmed: 28208702
Sci Rep. 2017 Mar 10;7:44373
pubmed: 28281653
J Bone Miner Res. 2020 Mar;35(3):550-570
pubmed: 31692093
Mol Cell Biol. 2009 May;29(10):2570-81
pubmed: 19273585
Autophagy. 2016 Sep;12(9):1631-46
pubmed: 27314664
J Bone Miner Res. 2020 Apr;35(4):725-737
pubmed: 31800975
EMBO J. 2014 Oct 1;33(19):2142-56
pubmed: 25107473
Matrix Biol. 2018 Sep;70:102-122
pubmed: 29605718
Cell Metab. 2013 May 7;17(5):719-30
pubmed: 23602449
J Biol Chem. 2008 Apr 18;283(16):10892-903
pubmed: 18281291
J Cell Physiol. 2010 Mar;222(3):648-57
pubmed: 19957303
J Cell Biol. 2016 Aug 1;214(3):333-45
pubmed: 27458135
Cell Death Differ. 2009 Jul;16(7):939-46
pubmed: 19229244
J Proteome Res. 2009 Oct;8(10):4844-50
pubmed: 19678709
Nat Cell Biol. 2012 Jan 22;14(2):177-85
pubmed: 22267086
Am J Physiol. 1998 May;274(5):E843-51
pubmed: 9612242
Cancer Res. 2001 Apr 15;61(8):3443-9
pubmed: 11309306
Dev Cell. 2019 Jun 3;49(5):748-763.e7
pubmed: 31105007
Cell Rep. 2015 Jul 7;12(1):116-127
pubmed: 26119730
Nature. 2015 May 28;521(7553):525-8
pubmed: 25896323
Trends Cell Biol. 2007 Nov;17(11):563-9
pubmed: 17959383
Pancreas. 2001 Jan;22(1):1-7
pubmed: 11138960
Annu Rev Physiol. 2016;78:505-31
pubmed: 26667075
J Cell Biochem. 2006 May 1;98(1):152-9
pubmed: 16408279
Nature. 2013 Dec 12;504(7479):291-5
pubmed: 24270810
Cell Death Differ. 2015 Sep;22(9):1399-401
pubmed: 26256515
Brain Res. 2017 Jul 1;1666:17-26
pubmed: 28438530
PLoS Biol. 2010 Jan 26;8(1):e1000298
pubmed: 20126261
Acta Histochem. 2017 Apr;119(3):315-326
pubmed: 28314612
Clin Orthop Relat Res. 2003 Jun;(411):315-24
pubmed: 12782890
Cell Death Differ. 2012 Jun;19(6):968-79
pubmed: 22139133
Am J Physiol Cell Physiol. 2007 Aug;293(2):C621-31
pubmed: 17442734
Neurol Res Int. 2015;2015:742059
pubmed: 26236504
Nature. 2019 Jun;570(7761):380-384
pubmed: 31092924
J Bone Miner Res. 2018 Feb;33(2):338-355
pubmed: 28940640
J Appl Physiol (1985). 2013 Nov;115(10):1562-71
pubmed: 23970537
PLoS One. 2014 Oct 22;9(10):e110768
pubmed: 25338007
Mol Cell. 2011 Nov 18;44(4):532-44
pubmed: 22099302
Curr Protoc Immunol. 2016 Apr 01;113:3.16B.1-3.16B.14
pubmed: 27038461
J Cell Sci. 2017 Sep 15;130(18):2953-2960
pubmed: 28842472
Ann Rheum Dis. 2011 Oct;70(10):1740-5
pubmed: 21646416
Anal Chim Acta. 2007 Feb 5;583(2):277-83
pubmed: 17386556