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The Mitochondrial Transacylase, Tafazzin, Regulates for AML Stemness by Modulating Intracellular Levels of Phospholipids.

ABSTRACT: 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.

SUBMITTER: Seneviratne AK 

PROVIDER: S-EPMC7137093 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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The Mitochondrial Transacylase, Tafazzin, Regulates for AML Stemness by Modulating Intracellular Levels of Phospholipids.

Seneviratne Ayesh K AK   Xu Mingjing M   Henao Juan J Aristizabal JJA   Fajardo Val A VA   Hao Zhenyue Z   Voisin Veronique V   Xu G Wei GW   Hurren Rose R   Kim S S   MacLean Neil N   Wang Xiaoming X   Gronda Marcela M   Jeyaraju Danny D   Jitkova Yulia Y   Ketela Troy T   Mullokandov Michael M   Sharon David D   Thomas Geethu G   Chouinard-Watkins Raphaël R   Hawley James R JR   Schafer Caitlin C   Yau Helen Loo HL   Khuchua Zaza Z   Aman Ahmed A   Al-Awar Rima R   Gross Atan A   Claypool Steven M SM   Bazinet Richard P RP   Lupien Mathieu M   Chan Steven S   De Carvalho Daniel D DD   Minden Mark D MD   Bader Gary D GD   Stark Ken D KD   LeBlanc Paul P   Schimmer Aaron D AD  

Cell stem cell 20190328 4

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 cardi  ...[more]

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