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

Role of PITRM1 in Mitochondrial Dysfunction and Neurodegeneration / D. Brunetti, A. Catania, C.F. Viscomi, M. Deleidi, L.A. Bindoff, D. Ghezzi, M. Zeviani. - In: BIOMEDICINES. - ISSN 2227-9059. - :9(2021), pp. 833.1-833.17. [10.3390/biomedicines9070833]

Role of PITRM1 in Mitochondrial Dysfunction and Neurodegeneration

D. Brunetti;C.F. Viscomi;D. Ghezzi;
2021

Abstract

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
PITRM1; pitrilysin metallopeptidase 1; mitochondrial proteostasis; Alzheimer Disease; neurodegeneration; neurodegenerative diseases; neurodegenerative dementia; spinocerebellar ataxia; mitochondrial protein quality control; protein aggregation; mitochondrial dysfunction
Settore BIO/14 - Farmacologia
Settore MED/03 - Genetica Medica
Settore BIO/13 - Biologia Applicata
Settore MED/26 - Neurologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/858353
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