Mitochondrial carrier homolog 2 is necessary for AML survival

Abstract

<jats:title>Abstract</jats:title> <jats:p>Through a clustered regularly insterspaced short palindromic repeats (CRISPR) screen to identify mitochondrial genes necessary for the growth of acute myeloid leukemia (AML) cells, we identified the mitochondrial outer membrane protein mitochondrial carrier homolog 2 (MTCH2). 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 (PDH), which 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.</jats:p>

Inhibition of Mitochondrial Carrier Homolog 2 (MTCH2) Suppresses Tumor Invasion and Enhances Sensitivity to Temozolomide in Malignant Glioma

“…6a-b). These results are supported by previous findings that MTCH2 suppresses mitochondrial fusion (18) and does not influence TCA cycle activity (23).…”

Multi-Tissue Neocortical Transcriptome-Wide Association Study Implicates 8 Genes Across 6 Genomic Loci in Alzheimer’s Disease

“…MTCH2 is known to contribute to adipocyte function, regulation of lipid metabolism [40,42], and to be genetically associated with obesity [43]. However, MTCH2 clearly has a role outside of adipocytes, as inhibition of MTCH2 increases products of metabolism, such as pyruvate and pyruvate dehydrogenase [44] in both brain and muscle. Our gene set enrichment analysis further supports MTCH2 involvement across a wide array of metabolic processes (Fig.…”

Inhibition of Mitochondrial Carrier Homolog 2 (MTCH2) Suppresses Tumor Invasion and Enhances Sensitivity to Temozolomide in Malignant Glioma&nbsp;

“…MTCH2 is a member of mitochondrial carrier family and regulates cell apoptosis by modulating the activity of mitochondrial permeability transition pore (37). Previous studies examined the role of MTCH2 in several types of tumors, including mammary carcinomas (21,22) and acute myeloid leukemia (AML) (23). Intriguingly, the role of MTCH2 in these tumors were opposite in breast cancer and AML.…”

“…A recent study showed the function of MTCH2 in acute myeloid leukemia (AML). Inhibiting MTCH2 decreased tumor growth and induced differentiation of AML cells (23). However, the role of MTCH2 in malignant glioma is not de ned.…”