Novel insights into Parkin-mediated mitochondrial dysfunction and neuroinflammation in Parkinson's disease

Sandro L Pereira; Dajana Grossmann; Sylvie Delcambre; Andreas Hermann; Anne Grünewald

doi:10.1016/j.conb.2023.102720

Novel insights into Parkin-mediated mitochondrial dysfunction and neuroinflammation in Parkinson's disease

Curr Opin Neurobiol. 2023 Jun:80:102720. doi: 10.1016/j.conb.2023.102720. Epub 2023 Apr 4.

Authors

Sandro L Pereira¹, Dajana Grossmann², Sylvie Delcambre¹, Andreas Hermann³, Anne Grünewald⁴

Affiliations

¹ Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg.
² Translational Neurodegeneration Section "Albrecht Kossel", Department of Neurology, University Medical Center Rostock, University of Rostock, Rostock, Germany.
³ Translational Neurodegeneration Section "Albrecht Kossel", Department of Neurology, University Medical Center Rostock, University of Rostock, Rostock, Germany; Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Rostock/Greifswald, 18147 Rostock, Germany; Center for Transdisciplinary Neurosciences Rostock (CTNR), University Medical Center Rostock, University of Rostock, 18147 Rostock, Germany.
⁴ Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg; Institute of Neurogenetics, University of Lübeck, Lübeck, Germany. Electronic address: anne.gruenewald@uni.lu.

PMID: 37023495
DOI: 10.1016/j.conb.2023.102720

Abstract

Mutations in PRKN cause the second most common genetic form of Parkinson's disease (PD)-a debilitating movement disorder that is on the rise due to population aging in the industrial world. PRKN codes for an E3 ubiquitin ligase that has been well established as a key regulator of mitophagy. Together with PTEN-induced kinase 1 (PINK1), Parkin controls the lysosomal degradation of depolarized mitochondria. But Parkin's functions go well beyond mitochondrial clearance: the versatile protein is involved in mitochondria-derived vesicle formation, cellular metabolism, calcium homeostasis, mitochondrial DNA maintenance, mitochondrial biogenesis, and apoptosis induction. Moreover, Parkin can act as a modulator of different inflammatory pathways. In the current review, we summarize the latest literature concerning the diverse roles of Parkin in maintaining a healthy mitochondrial pool. Moreover, we discuss how these recent discoveries may translate into personalized therapeutic approaches not only for PRKN-PD patients but also for a subset of idiopathic cases.

Keywords: Biogenesis; Calcium; Inflammation; Metabolism; Mitochondria; Mitophagy; PINK1; Parkin; Parkinson's disease; mtDNA.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Humans
Mitochondria / metabolism
Neuroinflammatory Diseases
Parkinson Disease* / genetics
Protein Kinases* / genetics
Protein Kinases* / metabolism
Ubiquitin-Protein Ligases / genetics
Ubiquitin-Protein Ligases / metabolism

Substances

Protein Kinases
Ubiquitin-Protein Ligases