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Pérez MJ, Ivanyuk D, Panagiotakopoulou V, et al. Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer's disease-like pathology in human cerebral organoids. Mol Psychiatry. 2020;26(10):5733-5750doi: 10.1038/s41380-020-0807-4.
Pérez, M. J., Ivanyuk, D., Panagiotakopoulou, V., Di Napoli, G., Kalb, S., Brunetti, D., Al-Shaana, R., Kaeser, S. A., Fraschka, S. A., Jucker, M., Zeviani, M., Viscomi, C., & Deleidi, M. (2021). Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer's disease-like pathology in human cerebral organoids. Molecular psychiatry, 26(10), 5733-5750. https://doi.org/10.1038/s41380-020-0807-4
Pérez, María José, et al. "Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer's disease-like pathology in human cerebral organoids." Molecular psychiatry vol. 26,10 (2021): 5733-5750. doi: https://doi.org/10.1038/s41380-020-0807-4
Pérez MJ, Ivanyuk D, Panagiotakopoulou V, Di Napoli G, Kalb S, Brunetti D, Al-Shaana R, Kaeser SA, Fraschka SA, Jucker M, Zeviani M, Viscomi C, Deleidi M. Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer's disease-like pathology in human cerebral organoids. Mol Psychiatry. 2021 Oct;26(10):5733-5750. doi: 10.1038/s41380-020-0807-4. Epub 2020 Jul 07. PMID: 32632204; PMCID: PMC8758476.
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Mol Psychiatry. 2021 Oct;26(10):5733-5750. doi: 10.1038/s41380-020-0807-4. Epub 2020 Jul 07.

Loss of function of the mitochondrial peptidase PITRM1 induces proteotoxic stress and Alzheimer's disease-like pathology in human cerebral organoids.

Molecular psychiatry

María José Pérez, Dina Ivanyuk, Vasiliki Panagiotakopoulou, Gabriele Di Napoli, Stefanie Kalb, Dario Brunetti, Rawaa Al-Shaana, Stephan A Kaeser, Sabine Anne-Kristin Fraschka, Mathias Jucker, Massimo Zeviani, Carlo Viscomi, Michela Deleidi

Affiliations

  1. German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
  2. Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
  3. Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy.
  4. Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
  5. DFG NGS Competence Center Tübingen, 72076, Tübingen, Germany.
  6. Institute of Medical Genetics and Applied Genomics, University of Tübingen, 72076, Tübingen, Germany.
  7. MRC-Mitochondrial Biology Unit, Cambridge, CB2 0XY, UK.
  8. German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. [email protected].
  9. Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. [email protected].

PMID: 32632204 PMCID: PMC8758476 DOI: 10.1038/s41380-020-0807-4

Abstract

Mutations in pitrilysin metallopeptidase 1 (PITRM1), a mitochondrial protease involved in mitochondrial precursor processing and degradation, result in a slow-progressing syndrome characterized by cerebellar ataxia, psychotic episodes, and obsessive behavior, as well as cognitive decline. To investigate the pathogenetic mechanisms of mitochondrial presequence processing, we employed cortical neurons and cerebral organoids generated from PITRM1-knockout human induced pluripotent stem cells (iPSCs). PITRM1 deficiency strongly induced mitochondrial unfolded protein response (UPR

© 2020. The Author(s).

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