ArticleEMBO molecular medicine2016
Defective PITRM1 mitochondrial peptidase is associated with Aβ amyloidotic neurodegeneration.
Article in EMBO molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 75 citations in OpenAlex.
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- Distributional genetic effects reveal context-dependent molecular regulation in human brain aging and Alzheimer's disease.Research square · 2025Article
- Quality control at the powerhouse: mitochondrial proteostasis dysfunction and disease.Biochemical Society transactions · 2025Article
- Organelle abnormalities in Alzheimer's disease.Organelle (Tucson, Ariz.) · 2025Article
- The Azalea Hypothesis of Alzheimer Disease: A Functional Iron Deficiency Promotes Neurodegeneration.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024Review
- Fetal and obstetrics manifestations of mitochondrial diseases.Journal of translational medicine · 2024Review
- Investigating copy number variants in schizophrenia pedigrees using a new consensus pipeline called PECAN.Scientific reports · 2024Article
- Profiling Protein-Protein Interactions in the Human Brain by Refined Cofractionation Mass Spectrometry.Journal of proteome research · 2024Article
- Neurotoxic β-amyloid oligomers cause mitochondrial dysfunction-the trigger for PANoptosis in neurons.Frontiers in aging neuroscience · 2024Review
- Mitophagy in Alzheimer's Disease: A Bibliometric Analysis from 2007 to 2022.Journal of Alzheimer's disease reports · 2024Article
- Decoding metabolic signatures in Alzheimer's disease: a mitochondrial perspective.Cell death discovery · 2023Review
- Red Flags in Primary Mitochondrial Diseases: What Should We Recognize?International journal of molecular sciences · 2023Review
- Exploring Whether Iron Sequestration within the CNS of Patients with Alzheimer's Disease Causes a Functional Iron Deficiency That Advances Neurodegeneration.Brain sciences · 2023Article
- Interactions of amyloidogenic proteins with mitochondrial protein import machinery in aging-related neurodegenerative diseases.Frontiers in physiology · 2023Review
- PPAR-gamma agonist pioglitazone recovers mitochondrial quality control in fibroblasts fromFrontiers in pharmacology · 2023Article
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21 authors at 8 institutions in 4 countries.
Funding
Abstract
Mitochondrial dysfunction and altered proteostasis are central features of neurodegenerative diseases. The pitrilysin metallopeptidase 1 (PITRM1) is a mitochondrial matrix enzyme, which digests oligopeptides, including the mitochondrial targeting sequences that are cleaved from proteins imported across the inner mitochondrial membrane and the mitochondrial fraction of amyloid beta (Aβ). We identified two siblings carrying a homozygous PITRM1 missense mutation (c.548G>A, p.Arg183Gln) associated with an autosomal recessive, slowly progressive syndrome characterised by mental retardation, spinocerebellar ataxia, cognitive decline and psychosis. The pathogenicity of the mutation was tested in vitro, in mutant fibroblasts and skeletal muscle, and in a yeast model. A Pitrm1(+/-) heterozygous mouse showed progressive ataxia associated with brain degenerative lesions, including accumulation of Aβ-positive amyloid deposits. Our results show that PITRM1 is responsible for significant Aβ degradation and that impairment of its activity results in Aβ accumulation, thus providing a mechanistic demonstration of the mitochondrial involvement in amyloidotic neurodegeneration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.