ATP-dependent Lon protease controls tumor bioenergetics by reprogramming mitochondrial activity
| Autor: | Clea Bárcena, Enrique Calvo, Kenta Watanabe, Rebeca Acín-Pérez, Pedro M. Quirós, Marta Loureiro, Yaiza Español, Antonio Fueyo, M. Soledad Fernández-García, Carlos López-Otín, José Antonio Enríquez, Jesús Vázquez, Francisco Rodríguez |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Redes Temáticas de Investigación Cooperativa en Salud (España), Fundación Cajastur, Japan Society for the Promotion of Science, Botín Foundation, Japan Society for the Promotion of Science (Japón) |
| Rok vydání: | 2013 |
| Předmět: |
Skin Neoplasms
Bioenergetics Homozygote Haploinsufficiency Biology HCT116 Cells Molecular biology General Biochemistry Genetics and Molecular Biology Oxidative Phosphorylation Mitochondria Mice HEK293 Cells lcsh:Biology (General) ATP-Dependent Proteases Lon Protease Cancer research Animals Humans Colorectal Neoplasms lcsh:QH301-705.5 Melanoma Cellular Senescence Gene Deletion Cell Proliferation |
| Zdroj: | Scopus RUO. Repositorio Institucional de la Universidad de Oviedo instname Cell Reports, Vol 8, Iss 2, Pp 542-556 (2014) Repisalud Instituto de Salud Carlos III (ISCIII) |
| ISSN: | 2211-1247 |
| Popis: | We generated mice deficient in Lon protease (LONP1), a major enzyme of the mitochondrial quality control machinery. Homozygous deletion of Lonp1 causes early embryonic lethality, whereas its haploinsufficiency protects against colorectal and skin tumors. Furthermore, LONP1 knockdown inhibits cellular proliferation and tumor and metastasis formation, whereas its overexpression increases tumorigenesis. Clinical studies indicate that high levels of LONP1 are a poor prognosis marker in human colorectal cancer and melanoma. Additionally, functional analyses show that LONP1 plays a key role in metabolic reprogramming by remodeling OXPHOS complexes and protecting against senescence. Our findings demonstrate the relevance of LONP1 for cellular and organismal viability and identify this protease as a central regulator of mitochondrial activity in oncogenesis. This work was supported by grants from the Ministerio de Economı´a y Competitividad, Instituto de Salud Carlos III (RTICC), and Red Tema´ tica de Investigacio´ n Cooperativa en Enfermedades Cardiovasculares. The Instituto Universitario de Oncologı´a is supported by Obra Social Cajastur. K.W. is supported by the Strategic Young Researcher Overseas Visits Program for Accelerating Brain Circulation from Japan Society for the Promotion of Science. C.L-O. is an investigator for the Botin Foundation. Sí |
| Databáze: | OpenAIRE |
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