Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Cell Stem Cell. 2019 Apr 4;24(4):621-636.e16. doi: 10.1016/j.stem.2019.02.020. Epub 2019 Mar 28.
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.
塔法辛（TAZ）是一种线粒体转酰基酶，可将线粒体心磷脂重塑为成熟形式。通过 CRISPR 筛选，我们发现 TAZ 对于急性髓系白血病（AML）细胞的生长和存活是必需的。TAZ 的基因抑制减少了 AML 细胞在体外和体内的干性和分化。相比之下，在基础条件下，TAZ 的敲低并不损害正常造血。从机制上讲，抑制 TAZ 降低了心磷脂的水平，但也改变了细胞内磷脂的整体水平，包括磷脂酰丝氨酸，它通过调节 Toll 样受体（TLR）信号来控制 AML 干性和分化。
