RESUMEN

CHCHD4 (MIA40) is central to the functions of the mitochondrial disulfide relay system (DRS). CHCHD4 is essential and evolutionarily conserved. Previously, we have shown CHCHD4 to be a critical regulator of tumour cell growth. Here, we use integrated analysis of our genome-wide CRISPR/Cas9 and SILAC proteomic screening data to delineate mechanisms of CHCHD4 essentiality in cancer. We identify a shortlist of common essential genes/proteins regulated by CHCHD4, including subunits of complex I that are known DRS substrates, and genes/proteins involved in key metabolic pathways. Our study highlights a range of CHCHD4-regulated nuclear encoded mitochondrial genes/proteins essential for tumour cell growth.

Asunto(s)

Regulación Neoplásica de la Expresión Génica , Mitocondrias , Neoplasias , Humanos , Neoplasias/genética , Neoplasias/patología , Neoplasias/metabolismo , Mitocondrias/metabolismo , Mitocondrias/genética , Proliferación Celular/genética , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Proteínas del Complejo de Importación de Proteínas Precursoras Mitocondriales , Genes Mitocondriales , Línea Celular Tumoral , Proteómica/métodos , Sistemas CRISPR-Cas , Proteínas de Transporte de Membrana Mitocondrial/genética , Proteínas de Transporte de Membrana Mitocondrial/metabolismo