title: Mitochondrial Lon protease at the crossroads of oxidative stress, ageing and cancer.
abstract: Lon protease is a nuclear DNA-encoded mitochondrial enzyme highly conserved throughout evolution, involved in the degradation of damaged and oxidized proteins of the mitochondrial matrix, in the correct folding of proteins imported in mitochondria, and in the maintenance of mitochondrial DNA. Lon expression is induced by various stimuli, including hypoxia and reactive oxygen species, and provides protection against cell stress. Lon down-regulation is associated with ageing and with cell senescence, while up-regulation is observed in tumour cells, and is correlated with a more aggressive phenotype of cancer. Lon up-regulation contributes to metabolic reprogramming observed in cancer, favours the switch from a respiratory to a glycolytic metabolism, helping cancer cell survival in the tumour microenvironment, and contributes to epithelial to mesenchymal transition. Silencing of Lon, or pharmacological inhibition of its activity, causes cell death in various cancer cells. Thus, Lon can be included in the growing class of proteins that are not responsible for oncogenic transformation, but that are essential for survival and proliferation of cancer cells, and that can be considered as a new target for development of anticancer drugs.
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi, 287, 41125, Modena, Italy. marcello.pinti@unimore.it.
authors.forename: Marcello
authors.identifier: http://orcid.org/0000-0001-9118-1262
authors.initials: M
authors.lastname: Pinti
authors.affiliation: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Gibellini
authors.affiliation: School of Life Sciences, Institute of Biophysics, Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
authors.forename: Yongzhang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Life Sciences, Institute of Biophysics, Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Xu
authors.affiliation: School of Life Sciences, Institute of Biophysics, Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Lu
authors.affiliation: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cossarizza
mesh_terms: D000375:Aging / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D053858:Metabolic Networks and Pathways; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D018384:Oxidative Stress; D049070:Protease La / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D024101:Mitochondrial Proteins; D049070:Protease La
keywords: Hypoxia; LONP1; Mitochondria; Pim1; mtDNA