Loss of the redox mitochondrial protein mitoNEET leads to mitochondrial dysfunction in B-cell acute lymphoblastic leukemia.
Chemoresistance
Glitazones
Mitochondrial dysfunction
cisd2
Journal
Free radical biology & medicine
ISSN: 1873-4596
Titre abrégé: Free Radic Biol Med
Pays: United States
ID NLM: 8709159
Informations de publication
Date de publication:
01 11 2021
01 11 2021
Historique:
received:
04
06
2021
revised:
28
08
2021
accepted:
04
09
2021
pubmed:
9
9
2021
medline:
1
10
2021
entrez:
8
9
2021
Statut:
ppublish
Résumé
B-cell acute lymphoblastic leukemia (ALL) affects both pediatric and adult patients. Chemotherapy resistant tumor cells that contribute to minimal residual disease (MRD) underlie relapse and poor clinical outcomes in a sub-set of patients. Targeting mitochondrial oxidative phosphorylation (OXPHOS) in the treatment of refractory leukemic cells is a potential novel approach to sensitizing tumor cells to existing standard of care therapeutic agents. In the current study, we have expanded our previous investigation of the mitoNEET ligand NL-1 in the treatment of ALL to interrogate the functional role of the mitochondrial outer membrane protein mitoNEET in B-cell ALL. Knockout (KO) of mitoNEET (gene: CISD1) in REH leukemic cells led to changes in mitochondrial ultra-structure and function. REH cells have significantly reduced OXPHOS capacity in the KO cells coincident with reduction in electron flow and increased reactive oxygen species. In addition, we found a decrease in lipid content in KO cells, as compared to the vector control cells was observed. Lastly, the KO of mitoNEET was associated with decreased proliferation as compared to control cells when exposed to the standard of care agent cytarabine (Ara-C). Taken together, these observations suggest that mitoNEET is essential for optimal function of mitochondria in B-cell ALL and may represent a novel anti-leukemic drug target for treatment of minimal residual disease.
Identifiants
pubmed: 34496224
pii: S0891-5849(21)00715-2
doi: 10.1016/j.freeradbiomed.2021.09.003
pmc: PMC8478879
mid: NIHMS1739917
pii:
doi:
Substances chimiques
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
226-235Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM109098
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM104942
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM121322
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103434
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM103488
Pays : United States
Organisme : NIH HHS
ID : S10 OD016165
Pays : United States
Organisme : NCRR NIH HHS
ID : P20 RR016440
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL128485
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Références
Biochem Biophys Res Commun. 1969 Sep 10;36(6):905-11
pubmed: 4310147
Proc Natl Acad Sci U S A. 2019 Oct 1;116(40):19924-19929
pubmed: 31527235
Nat Med. 2012 Oct;18(10):1539-49
pubmed: 22961109
Br J Cancer. 2002 Mar 18;86(6):963-70
pubmed: 11953830
Proc Natl Acad Sci U S A. 2013 Sep 3;110(36):14676-81
pubmed: 23959881
Nat Commun. 2020 Aug 13;11(1):4056
pubmed: 32792483
Mitochondrion. 2019 Nov;49:259-268
pubmed: 31207408
Biology (Basel). 2021 Jan 22;10(2):
pubmed: 33499222
PLoS One. 2016 May 31;11(5):e0156054
pubmed: 27243905
Int J Mol Sci. 2021 May 07;22(9):
pubmed: 34066940
Methods Enzymol. 2009;456:233-46
pubmed: 19348892
Am J Physiol Endocrinol Metab. 2004 Feb;286(2):E252-60
pubmed: 14570702
Cell Metab. 2020 Sep 1;32(3):341-352
pubmed: 32668195
Cancer Res. 2008 Jul 1;68(13):5198-205
pubmed: 18593920
J Vis Exp. 2016 Feb 09;(108):e53645
pubmed: 26891147
Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14342-7
pubmed: 17766440
Oncotarget. 2017 Jun 28;8(40):67639-67650
pubmed: 28978059
Biochim Biophys Acta Bioenerg. 2017 Aug;1858(8):686-699
pubmed: 28161329
Biochem Biophys Res Commun. 2011 Jun 3;409(2):241-6
pubmed: 21570952
Free Radic Res. 2020 Jun;54(6):397-407
pubmed: 32605459
BMC Cancer. 2021 May 31;21(1):645
pubmed: 34059009
Transl Oncol. 2021 May;14(5):101048
pubmed: 33667892
PeerJ. 2021 Apr 13;9:e11233
pubmed: 33954048
Antioxid Redox Signal. 2019 Mar 10;30(8):1083-1095
pubmed: 29463105
Cell Death Differ. 2008 Jul;15(7):1147-52
pubmed: 18437161
J Biol Chem. 1994 Oct 21;269(42):26443-8
pubmed: 7929365
ACS Chem Neurosci. 2017 Dec 20;8(12):2759-2765
pubmed: 28880525
Biochem Pharmacol. 2014 Nov 1;92(1):62-72
pubmed: 25107705
J Biol Chem. 2017 Jun 16;292(24):10061-10067
pubmed: 28461337
Leuk Lymphoma. 2018 Nov;59(11):2535-2545
pubmed: 29431560
Cell Cycle. 2012 Nov 15;11(22):4174-80
pubmed: 23070475
Nat Med. 2017 Oct;23(10):1234-1240
pubmed: 28920959
Pharm Res. 2020 Jan 27;37(3):43
pubmed: 31989336
Metabolomics. 2006;2(1):21-29
pubmed: 24489530
Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5318-23
pubmed: 17376863
Diabetes. 2016 Jun;65(6):1534-55
pubmed: 26895793
J Biol Inorg Chem. 2018 Jun;23(4):599-612
pubmed: 29435647
Proc Natl Acad Sci U S A. 2015 Mar 24;112(12):3698-703
pubmed: 25762074
Sci Rep. 2021 Aug 4;11(1):15840
pubmed: 34349149
Biochim Biophys Acta Bioenerg. 2017 Aug;1858(8):655-664
pubmed: 28088333
Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):5422-7
pubmed: 23513224
Clin Cancer Res. 2014 Aug 1;20(15):4014-25
pubmed: 24833663
Sci Rep. 2017 Feb 16;7:42571
pubmed: 28205535
Front Cell Dev Biol. 2021 Jun 24;9:616271
pubmed: 34249899
Biochim Biophys Acta Rev Cancer. 2021 Apr;1875(2):188518
pubmed: 33545296
Naunyn Schmiedebergs Arch Pharmacol. 2021 Feb;394(2):361-371
pubmed: 33015747
J Biol Chem. 2007 Aug 17;282(33):23745-9
pubmed: 17584744
Cell Stem Cell. 2021 Apr 1;28(4):702-717.e8
pubmed: 33539722
Methods Mol Biol. 2012;810:183-205
pubmed: 22057568
Cell Death Discov. 2021 May 4;7(1):93
pubmed: 33947836
J Biol Chem. 2014 Feb 14;289(7):4307-15
pubmed: 24403080
Free Radic Biol Med. 2017 Jan;102:240-247
pubmed: 27923678
J Clin Endocrinol Metab. 2007 Jan;92(1):166-71
pubmed: 17062758
Drug Discov Today. 2014 Oct;19(10):1601-6
pubmed: 24814435
Tumour Biol. 2020 Oct;42(10):1010428320965284
pubmed: 33028168
J Pharmacol Exp Ther. 2019 Jul;370(1):25-34
pubmed: 31010844