Reference : The Emerging Role of RHOT1/Miro1 in the Pathogenesis of Parkinson's Disease.
Scientific journals : Article
Life sciences : Genetics & genetic processes
Systems Biomedicine
http://hdl.handle.net/10993/45259
The Emerging Role of RHOT1/Miro1 in the Pathogenesis of Parkinson's Disease.
English
Grossmann, Dajana [Universitätsmedizin Rostock > Department of Neurology]
Berenguer-Escuder, Clara [> >]
Chemla, Axel mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience]
Arena, Giuseppe mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience]
Krüger, Rejko mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Translational Neuroscience]
2020
Frontiers in neurology
11
587
Yes (verified by ORBilu)
International
1664-2295
1664-2295
[en] Miro1 ; Parkinson's disease ; calcium signaling ; mitochondrial dynamics ; mitophagy
[en] The expected increase in prevalence of Parkinson's disease (PD) as the most common neurodegenerative movement disorder over the next years underscores the need for a better understanding of the underlying molecular pathogenesis. Here, first insights provided by genetics over the last two decades, such as dysfunction of molecular and organellar quality control, are described. The mechanisms involved relate to impaired intracellular calcium homeostasis and mitochondrial dynamics, which are tightly linked to the cross talk between the endoplasmic reticulum (ER) and mitochondria. A number of proteins related to monogenic forms of PD have been mapped to these pathways, i.e., PINK1, Parkin, LRRK2, and α-synuclein. Recently, Miro1 was identified as an important player, as several studies linked Miro1 to mitochondrial quality control by PINK1/Parkin-mediated mitophagy and mitochondrial transport. Moreover, Miro1 is an important regulator of mitochondria-ER contact sites (MERCs), where it acts as a sensor for cytosolic calcium levels. The involvement of Miro1 in the pathogenesis of PD was recently confirmed by genetic evidence based on the first PD patients with heterozygous mutations in RHOT1/Miro1. Patient-based cellular models from RHOT1/Miro1 mutation carriers showed impaired calcium homeostasis, structural alterations of MERCs, and increased mitochondrial clearance. To account for the emerging role of Miro1, we present a comprehensive overview focusing on the role of this protein in PD-related neurodegeneration and highlighting new developments in our understanding of Miro1, which provide new avenues for neuroprotective therapies for PD patients.
Researchers ; Professionals ; Students
http://hdl.handle.net/10993/45259
10.3389/fneur.2020.00587
https://www.frontiersin.org/articles/10.3389/fneur.2020.00587/full
OA
Copyright © 2020 Grossmann, Berenguer-Escuder, Chemla, Arena and Krüger.
FnR ; FNR11676395 > Rejko Krüger > MiRisk-PD > Mitochondrial Risk factors in Parkinson's Disease > 01/03/2018 > 28/02/2021 > 2017

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