CHCHD4 regulates the expression of mitochondrial genes that are essential for tumour cell growth.

Thomas, Luke W; Stephen, Jenna M; Ashcroft, Margaret

Thomas, Luke W; Stephen, Jenna M; Ashcroft, Margaret.

Afiliación

Thomas LW; Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, United Kingdom.
Stephen JM; Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, United Kingdom.
Ashcroft M; Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0QQ, United Kingdom. Electronic address: m.ashcroft@medschl.cam.ac.uk.

Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167282, 2024 10.

Article en En | MEDLINE | ID: mdl-38909850

ABSTRACT

ABSTRACT

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

Palabras clave

CHCHD4; CRISPR/Cas9 genome-wide deletion screen; Gene essentiality; Mitochondria; Proteomics; SILAC analysis

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación Neoplásica de la Expresión Génica / Mitocondrias / Neoplasias Límite: Humans Idioma: En Revista: Biochim Biophys Acta Mol Basis Dis Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Países Bajos

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