The Mitochondrial Transacylase, Tafazzin, Regulates for AML Stemness by Modulating Intracellular Levels of Phospholipids.
Acyltransferases
Animals
Cell Line, Tumor
Doxorubicin
/ pharmacology
Female
Humans
Leukemia, Myeloid, Acute
/ metabolism
Male
Mice
Mice, Inbred NOD
Mice, SCID
Mice, Transgenic
Mitochondria
/ enzymology
Phospholipids
/ metabolism
Signal Transduction
/ drug effects
Toll-Like Receptors
/ metabolism
Transcription Factors
/ antagonists & inhibitors
acute myeloid leukemia
cancer differentiation
cardiolipin
leukemia initiating cell
mitochondria
phosphatidylserine
phospholipids
tafazzin
Journal
Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472
Informations de publication
Date de publication:
04 04 2019
04 04 2019
Historique:
received:
12
06
2018
revised:
19
12
2018
accepted:
27
02
2019
pubmed:
2
4
2019
medline:
19
5
2020
entrez:
2
4
2019
Statut:
ppublish
Résumé
Tafazzin (TAZ) is a mitochondrial transacylase that remodels the mitochondrial cardiolipin into its mature form. Through a CRISPR screen, we identified TAZ as necessary for the growth and viability of acute myeloid leukemia (AML) cells. Genetic inhibition of TAZ reduced stemness and increased differentiation of AML cells both in vitro and in vivo. In contrast, knockdown of TAZ did not impair normal hematopoiesis under basal conditions. Mechanistically, inhibition of TAZ decreased levels of cardiolipin but also altered global levels of intracellular phospholipids, including phosphatidylserine, which controlled AML stemness and differentiation by modulating toll-like receptor (TLR) signaling.
Identifiants
pubmed: 30930145
pii: S1934-5909(19)30072-4
doi: 10.1016/j.stem.2019.02.020
pmc: PMC7137093
mid: NIHMS1577414
pii:
doi:
Substances chimiques
Phospholipids
0
Toll-Like Receptors
0
Transcription Factors
0
Doxorubicin
80168379AG
Acyltransferases
EC 2.3.-
TAFAZZIN protein, human
EC 2.3.1.-
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
621-636.e16Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM111548
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG009979
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL108882
Pays : United States
Organisme : CIHR
Pays : Canada
Commentaires et corrections
Type : ErratumIn
Informations de copyright
Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.
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