Mitochondrial carrier homolog 2 (MTCH2) is necessary for AML survival.

Through a CRISPR screen to identify mitochondrial genes necessary for the growth of AML cells, we identified the mitochondrial outer membrane protein MTCH2 (Mitochondrial Carrier Homolog 2). In AML, knockdown of MTCH2 decreased growth, reduced engraftment potential of stem cells and induced differentiation. Inhibiting MTCH2 in AML cells increased nuclear pyruvate and pyruvate dehydrogenase that induced histone acetylation and subsequently promoted the differentiation of AML cells. Thus, we have defined a new mechanism by which mitochondria and metabolism regulate AML stem cells and gene expression.