| Autor: |
Pedro M. Quirós, Yaiza Español, Rebeca Acín-Pérez, Francisco Rodríguez, Clea Bárcena, Kenta Watanabe, Enrique Calvo, Marta Loureiro, M. Soledad Fernández-García, Antonio Fueyo, Jesús Vázquez, José Antonio Enríquez, Carlos López-Otín |
| Jazyk: |
angličtina |
| Rok vydání: |
2014 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 8, Iss 2, Pp 542-556 (2014) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2014.06.018 |
| 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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