Article (Scientific journals)
The genetic architecture of mitochondrial dysfunction in Parkinson's Disease
Krüger, Rejko; Larsen, Simone; Hanss, Zoé
2018In Cell and Tissue Research
Peer reviewed


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Keywords :
mitochondrial; dysfunction; parkinson's
Abstract :
[en] Mitochondrial impairment is a well-established pathological pathway implicated in Parkinson’s disease (PD). Defects of the complex I of the mitochondrial respiratory chain have been found in post mortem brains from sporadic PD patients. Furthermore, several disease-related genes are linked to mitochondrial pathways, such as PRKN, PINK1, DJ-1 and HTRA2 and are associated to mitochondrial impairment. This phenotype can be caused by the dysfunction of mitochondrial quality control machinery at different levels: molecular, organellar or cellular. Mitochondrial unfolded protein response represents the molecular level and implicates various chaperones and proteases. If the molecular level of quality control is not sufficient, the organellar level is required and involves mitophagy and mitochondrial derived vesicles to sequester whole dysfunctional organelle or parts of it. Only when the impairment is too severe, it leads to cell death via apoptosis which defines the cellular level of quality control. Here we review how currently known PD-linked genetic variants interfere with the different levels of mitochondrial quality control. We discuss the graded risk concept of the most recently identified PARK loci (PARK 17-23) and some susceptibility variants such as GBA, LRRK2 and SNCA. Finally, the emerging concept of rare genetic variants as candidates for PD, such as HSPA9, TRAP1 and RHOT1 complete the picture of the complex genetic architecture of PD that will direct future precision medicine approaches.
Research center :
Luxembourg Centre for Systems Biomedicine (LCSB)
Disciplines :
Author, co-author :
Krüger, Rejko ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Larsen, Simone ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Hanss, Zoé ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
External co-authors :
Language :
Title :
The genetic architecture of mitochondrial dysfunction in Parkinson's Disease
Publication date :
January 2018
Journal title :
Cell and Tissue Research
Publisher :
Peer reviewed :
Peer reviewed
FnR Project :
FNR6682797 - Comprehensive Assessment Of Endophenotypes In Neurodegenerative Diseases - Translating Impaired Molecular Signalling Pathways Into Novel Therapeutic Strategies For Parkinson'S Disease, 2013 (01/06/2014-31/05/2019) - Rejko Krüger
Funders :
FNR - Fonds National de la Recherche [LU]
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