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Cell Rep. 2014 Jul 24;8(2):542-56. doi: 10.1016/j.celrep.2014.06.018. Epub 2014 Jul 10.

ATP-dependent Lon protease controls tumor bioenergetics by reprogramming mitochondrial activity.

Author information

1
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006 Oviedo, Spain.
2
Department of Cardiovascular Development and Repair, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain.
3
Cardiovascular Proteomics Laboratory, Department of Vascular Biology, Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain.
4
Servicio de Anatomía Patológica, Hospital Universitario Central de Asturias, 33006 Oviedo, Spain.
5
Area de Fisiología, Departamento de Biología Funcional, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006 Oviedo, Spain.
6
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006 Oviedo, Spain. Electronic address: clo@uniovi.es.

Abstract

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.

PMID:
25017063
DOI:
10.1016/j.celrep.2014.06.018
[Indexed for MEDLINE]
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