New Collaborative MPB Publication led by Dr. Aaron Schimmer
A team lead by MBP researcher Dr. Aaron Schimmer, which includes MBP researchers Dr. Daniel De Carvalho, Dr. Steven Chan, Dr. Mathieu Lupien, and Dr. Mark Minden, have released a new publication titled "The Mitochondrial Transacylase, Tafazzin, Regulates for AML Stemness by Modulating Intracellular Levels of Phospholipids".
Tafazzin (TAZ) is a mitochondrial transacylase that remodels the mitochondrial cardiolipin into its mature form. Through a CRISPR screen, they 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.
Highlights
- Inhibiting TAZ leads to increased levels of PS in AML cells
- TAZ and PS regulate AML stemness
- Reducing TAZ or increasing PS decreases AML stemness and activates TLR signaling
- Increasing PS is a potential therapeutic strategy for AML