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Review

Role of PITRM1 in Mitochondrial Dysfunction and Neurodegeneration

1
Department of Medical Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy
2
Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20126 Milan, Italy
3
Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy
4
German Center for Neurodegenerative Diseases (DZNE), 72076 Tübingen, Germany
5
Neuro-SysMed, Center of Excellence for Clinical Research in Neurological Diseases, Haukeland University Hospital, N-5021 Bergen, Norway
6
Department of Clinical Medicine, University of Bergen, N-5021 Bergen, Norway
7
Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
8
Department of Neurosciences, University of Padova, 35128 Padova, Italy
9
Venetian Institute of Molecular Medicine, 35128 Padova, Italy
*
Authors to whom correspondence should be addressed.
Academic Editor: Susana Cardoso
Received: 7 June 2021 / Revised: 13 July 2021 / Accepted: 15 July 2021 / Published: 17 July 2021
(This article belongs to the Special Issue Mitochondria and Brain Disease)
Mounting evidence shows a link between mitochondrial dysfunction and neurodegenerative disorders, including Alzheimer Disease. Increased oxidative stress, defective mitodynamics, and impaired oxidative phosphorylation leading to decreased ATP production, can determine synaptic dysfunction, apoptosis, and neurodegeneration. Furthermore, mitochondrial proteostasis and the protease-mediated quality control system, carrying out degradation of potentially toxic peptides and misfolded or damaged proteins inside mitochondria, are emerging as potential pathogenetic mechanisms. The enzyme pitrilysin metallopeptidase 1 (PITRM1) is a key player in these processes; it is responsible for degrading mitochondrial targeting sequences that are cleaved off from the imported precursor proteins and for digesting a mitochondrial fraction of amyloid beta (Aβ). In this review, we present current evidence obtained from patients with PITRM1 mutations, as well as the different cellular and animal models of PITRM1 deficiency, which points toward PITRM1 as a possible driving factor of several neurodegenerative conditions. Finally, we point out the prospect of new diagnostic and therapeutic approaches. View Full-Text
Keywords: PITRM1; pitrilysin metallopeptidase 1; mitochondrial proteostasis; Alzheimer Disease; neurodegeneration; neurodegenerative diseases; neurodegenerative dementia; spinocerebellar ataxia; mitochondrial protein quality control; protein aggregation; mitochondrial dysfunction PITRM1; pitrilysin metallopeptidase 1; mitochondrial proteostasis; Alzheimer Disease; neurodegeneration; neurodegenerative diseases; neurodegenerative dementia; spinocerebellar ataxia; mitochondrial protein quality control; protein aggregation; mitochondrial dysfunction
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MDPI and ACS Style

Brunetti, D.; Catania, A.; Viscomi, C.; Deleidi, M.; Bindoff, L.A.; Ghezzi, D.; Zeviani, M. Role of PITRM1 in Mitochondrial Dysfunction and Neurodegeneration. Biomedicines 2021, 9, 833. https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9070833

AMA Style

Brunetti D, Catania A, Viscomi C, Deleidi M, Bindoff LA, Ghezzi D, Zeviani M. Role of PITRM1 in Mitochondrial Dysfunction and Neurodegeneration. Biomedicines. 2021; 9(7):833. https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9070833

Chicago/Turabian Style

Brunetti, Dario, Alessia Catania, Carlo Viscomi, Michela Deleidi, Laurence A. Bindoff, Daniele Ghezzi, and Massimo Zeviani. 2021. "Role of PITRM1 in Mitochondrial Dysfunction and Neurodegeneration" Biomedicines 9, no. 7: 833. https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines9070833

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