CHCHD4 regulates tumour proliferation and EMT-related phenotypes, through respiratory chain-mediated metabolism.
Coiled-coil helix coiled-coil helix domain-containing protein 4 (CHCHD4)
HIF-1α
complex I
disulfide relay system
hypoxia
mitochondria
respiratory chain
tumour growth
tumour metabolism
Journal
Cancer & metabolism
ISSN: 2049-3002
Titre abrégé: Cancer Metab
Pays: England
ID NLM: 101607582
Informations de publication
Date de publication:
2019
2019
Historique:
received:
31
01
2019
accepted:
26
06
2019
entrez:
27
7
2019
pubmed:
28
7
2019
medline:
28
7
2019
Statut:
epublish
Résumé
Mitochondrial oxidative phosphorylation (OXPHOS) via the respiratory chain is required for the maintenance of tumour cell proliferation and regulation of epithelial to mesenchymal transition (EMT)-related phenotypes through mechanisms that are not fully understood. The essential mitochondrial import protein coiled-coil helix coiled-coil helix domain-containing protein 4 (CHCHD4) controls respiratory chain complex activity and oxygen consumption, and regulates the growth of tumours in vivo. In this study, we interrogate the importance of CHCHD4-regulated mitochondrial metabolism for tumour cell proliferation and EMT-related phenotypes, and elucidate key pathways involved. Using in silico analyses of 967 tumour cell lines, and tumours from different cancer patient cohorts, we show that CHCHD4 drives tumour cell growth and activates mTORC1 signalling through its control of respiratory chain mediated metabolism and complex I biology, and also regulates EMT-related phenotypes of tumour cells.
Sections du résumé
BACKGROUND
BACKGROUND
Mitochondrial oxidative phosphorylation (OXPHOS) via the respiratory chain is required for the maintenance of tumour cell proliferation and regulation of epithelial to mesenchymal transition (EMT)-related phenotypes through mechanisms that are not fully understood. The essential mitochondrial import protein coiled-coil helix coiled-coil helix domain-containing protein 4 (CHCHD4) controls respiratory chain complex activity and oxygen consumption, and regulates the growth of tumours in vivo. In this study, we interrogate the importance of CHCHD4-regulated mitochondrial metabolism for tumour cell proliferation and EMT-related phenotypes, and elucidate key pathways involved.
RESULTS
RESULTS
Using in silico analyses of 967 tumour cell lines, and tumours from different cancer patient cohorts, we show that
CONCLUSIONS
CONCLUSIONS
CHCHD4 drives tumour cell growth and activates mTORC1 signalling through its control of respiratory chain mediated metabolism and complex I biology, and also regulates EMT-related phenotypes of tumour cells.
Identifiants
pubmed: 31346464
doi: 10.1186/s40170-019-0200-4
pii: 200
pmc: PMC6632184
doi:
Types de publication
Journal Article
Langues
eng
Pagination
7Subventions
Organisme : Medical Research Council
ID : MC_UU_12022/6
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K002201/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/K002201/2
Pays : United Kingdom
Déclaration de conflit d'intérêts
Competing interestsThe authors declare that they have no competing interests.
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