Role of pitrm1 in mitochondrial dysfunction and neurodegeneration

Dario Brunetti, Alessia Catania, Carlo Viscomi, Michela Deleidi, Laurence A. Bindoff, Daniele Ghezzi, Massimo Zeviani

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish
Article number833
Issue number7
Publication statusPublished - Jul 2021


  • Alzheimer Disease
  • Mitochondrial dysfunction
  • Mitochondrial protein quality control
  • Mitochondrial proteostasis
  • Neurodegeneration
  • Neurodegenerative dementia
  • Neurodegenerative diseases
  • Pitrilysin metallopeptidase 1
  • PITRM1
  • Protein aggregation
  • Spinocerebellar ataxia

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'Role of pitrm1 in mitochondrial dysfunction and neurodegeneration'. Together they form a unique fingerprint.

Cite this