caa a22 4500 606176187 CHVBK 20210128100746.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s00018-015-2039-3 doi (NATIONALLICENCE)springer-10.1007/s00018-015-2039-3 Mitochondrial Lon protease at the crossroads of oxidative stress, ageing and cancer [Elektronische Daten] [Marcello Pinti, Lara Gibellini, Yongzhang Liu, Shan Xu, Bin Lu, Andrea Cossarizza] 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. Springer Basel, 2015 LONP1 nationallicence Pim1 nationallicence Mitochondria nationallicence Hypoxia nationallicence mtDNA nationallicence AAA+ : ATPase associated with diverse cellular activities nationallicence Aco2 : Aconitase 2 nationallicence ALAS-1 : 5-aminolevulinic acid synthase 1 nationallicence AOX : acyl-CoA oxidase nationallicence cART : Combined antiretroviral therapy nationallicence C/EBP : CCAAT-enhancer-binding protein nationallicence CBS : Cystathionine β-synthase nationallicence CDDO-Me : 2-cyano-3, 12-dioxoo- leana-1,9(11)-dien-28-oic methyl ester nationallicence CDDO : 2-cyano-3, 12-dioxoo- leana-1,9(11)-dien-28-oic acid nationallicence CHOP : C/EBP homology protein nationallicence Clp : Caseinolytic protease nationallicence ClpX : Caseinolytic protease X nationallicence cLβL : Clasto-lactacystin β-lactone nationallicence CODAS : Cerebral, ocular, dental, auricular and skeletal anomalies nationallicence COX : Cytochrome c oxidase nationallicence COX4-1 : Cytochrome c oxidase, subunit 4, isoform 1 nationallicence CR : Caloric restriction nationallicence EMT : Epithelial-mesenchymal transition nationallicence ER : Endoplasmic reticulum nationallicence ERK1 : Extracellular-signal-regulated kinase 1 nationallicence ERK2 : Extracellular-signal-regulated kinase 2 nationallicence FITC : Fluorescein isothiocyanate nationallicence GLS-1 : Glutaminase C nationallicence HIF1-α : Hypoxia inducible factor 1 α nationallicence HIV : Human immunodeficiency virus nationallicence JNK : c-Jun N-terminal kinase nationallicence LONP1 : Lon peptidase 1, mitochondrial nationallicence Lyf-1 : Lymphoid transcription factor nationallicence m-AAA : Matrix-ATPase associated with diverse cellular activities nationallicence MELAS : Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes nationallicence MERRF : Myoclonic epilepsy with ragged-red fibre nationallicence MMP-2 : Matrix metalloproteinase-2 nationallicence MnSOD : Manganese superoxide dismutase nationallicence mtDNA : Mitochondrial DNA nationallicence MTS : Mitochondrial-targeting sequence nationallicence NDFUS3 : NADH dehydrogenase (ubiquinone) Fe-S protein 3 nationallicence NDFUS7 : NADH dehydrogenase (ubiquinone) Fe-S protein 7 nationallicence NDFUS8 : NADH dehydrogenase (ubiquinone) Fe-S protein 8 nationallicence NDUFB6 : NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 6 nationallicence NDUFV1 : NADH dehydrogenase (ubiquinone) flavoprotein 1 nationallicence NDUFV2 : NADH dehydrogenase (ubiquinone) flavoprotein 2 nationallicence NF-kB : Nuclear factor kappa-B nationallicence Nkx2-5 : NK2 homeobox 5 nationallicence NRF1 : Nuclear respiratory factor 1 nationallicence NRF2 : Nuclear respiratory factor 2 nationallicence NRTI : Nucleotide analogue reverse transcriptase inhibitor nationallicence OA : Obtusilactone A nationallicence OCR : Oxygen consumption rate nationallicence OXPHOS : Oxidative phosphorylation nationallicence PGC1 α : Peroxisome proliferator-activated receptor γ coactivator 1 α nationallicence Pim1 : Proteolysis into mitochondria 1 nationallicence PMP70 : 70-kDa peroxisomal membrane protein nationallicence PMSF : Phenylmethanesulphonylfluoride nationallicence POLDIP2 : Polymerase (DNA-directed) delta interacting protein 2 nationallicence PRSS15 : Serine protease 15 nationallicence PI : Protease inhibitor nationallicence PTS1 : Peroxisomal targeting sequence type-1 nationallicence ROS : Reactive oxygen species nationallicence SDH : Succinate dehydrogenase nationallicence SDH5 : Succinate dehydrogenase 5 nationallicence SDHA : Succinate dehydrogenase complex, subunit A nationallicence SIRT1 : Sirtuin 1 nationallicence SIRT3 : Sirtuin 3 nationallicence StAR : Steroidogenic acute regulatory protein nationallicence TCA cycle : Tricarboxylic acid cycle nationallicence TFAM : Mitochondrial transcription factor A nationallicence Tysnd1 : Trypsin domain containing 1 nationallicence VHL : Von Hippel Lindau tumour suppressor nationallicence Pinti Marcello Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi, 287, 41125, Modena, Italy aut Gibellini Lara Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy aut Liu Yongzhang School of Life Sciences, Institute of Biophysics, Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China aut Xu Shan School of Life Sciences, Institute of Biophysics, Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China aut Lu Bin School of Life Sciences, Institute of Biophysics, Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China aut Cossarizza Andrea Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy aut Cellular and Molecular Life Sciences Springer International Publishing 72/24(2015-12-01), 4807-4824 1420-682X 72:24<4807 2015 72 18 https://doi.org/10.1007/s00018-015-2039-3 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-2039-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Pinti Marcello Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi, 287, 41125, Modena, Italy aut NATIONALLICENCE 700 1- Gibellini Lara Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy aut NATIONALLICENCE 700 1- Liu Yongzhang School of Life Sciences, Institute of Biophysics, Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China aut NATIONALLICENCE 700 1- Xu Shan School of Life Sciences, Institute of Biophysics, Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China aut NATIONALLICENCE 700 1- Lu Bin School of Life Sciences, Institute of Biophysics, Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, 325035, Wenzhou, Zhejiang, China aut NATIONALLICENCE 700 1- Cossarizza Andrea Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer International Publishing 72/24(2015-12-01), 4807-4824 1420-682X 72:24<4807 2015 72 18