title: Mitochondrial Proteases as Emerging Pharmacological Targets.
abstract: The preservation of mitochondrial function and integrity is critical for cell viability. Under stress conditions, unfolded, misfolded or damaged proteins accumulate in a certain compartment of the organelle, interfering with oxidative phosphorylation and normal mitochondrial functions. In stress conditions, several mechanisms, including mitochondrial unfolded protease response (UPRmt), fusion and fission, and mitophagy are engaged to restore normal proteostasis of the organelle. Mitochondrial proteases are a family of more than 20 enzymes that not only are involved in the UPRmt, but actively participate at multiple levels in the stress-response system. Alterations in their expression levels, or mutations that determine loss or gain of function of these proteases deeply impair mitochondrial functionality and can be associated with the onset of inherited diseases, with the development of neurodegenerative disorders and with the process of carcinogenesis. In this review, we focus our attention on six of them, namely CLPP, HTRA2 and LONP1, by analysing the current knowledge about their functions, their involvement in the pathogenesis of human diseases, and the compounds currently available for inhibiting their functions.
authors.forename: Lara
authors.initials: L
authors.lastname: Gibellini
authors.forename: Sara
authors.initials: S
authors.lastname: De Biasi
authors.forename: Milena
authors.initials: M
authors.lastname: Nasi
authors.forename: Anna
authors.initials: A
authors.lastname: Iannone
authors.forename: Andrea
authors.initials: A
authors.lastname: Cossarizza
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.initials: M
authors.lastname: Pinti
mesh_terms: D000818:Animals; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D058767:Protein Unfolding / Q000187:drug effects
chemical_list: D047428:Protein Kinase Inhibitors; D010447:Peptide Hydrolases