Mitochondrial Regulation of GPX4 Inhibition-Mediated Ferroptosis in Acute Myeloid Leukemia

Authors

Hiroki Akiyama
Ran Zhao
Lauren B Ostermann
Ziyi Li
Matthew Tcheng
Samar J Yazdani
Arman Moayed
Malcolm L Pryor
Sandeep Slngh
Natalia Baran
Edward Ayoub
Yuki Nishida
Po Yee Mak
Vivian R Ruvolo
Bing Z Carter
Aaron D Schimmer
Michael Andreeff
Jo Ishizawa

Publication Date

4-1-2024

Journal

Leukemia

Abstract

Resistance to apoptosis in acute myeloid leukemia (AML) cells causes refractory or relapsed disease, associated with dismal clinical outcomes. Ferroptosis, a mode of non-apoptotic cell death triggered by iron-dependent lipid peroxidation, has been investigated as potential therapeutic modality against therapy-resistant cancers, but our knowledge of its role in AML is limited. We investigated ferroptosis in AML cells and identified its mitochondrial regulation as a therapeutic vulnerability. GPX4 knockdown induced ferroptosis in AML cells, accompanied with characteristic mitochondrial lipid peroxidation, exerting anti-AML effects in vitro and in vivo. Electron transport chains (ETC) are primary sources of coenzyme Q

Keywords

Humans, Ferroptosis, Mitochondria, Lipids, Leukemia, Myeloid, Acute, Peptide Hydrolases

DOI

10.1038/s41375-023-02117-2

PMID

38148395

PMCID

PMC11082873

PubMedCentral® Posted Date

May 2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes