Parkin, an E3 Ubiquitin Ligase, Plays an Essential Role in Mitochondrial Quality Control in Parkinson’s Disease

2020 ◽  
Author(s):  
Xiao-Le Wang ◽  
Si-Tong Feng ◽  
Zhen-Zhen Wang ◽  
Yu-He Yuan ◽  
Nai-Hong Chen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Quality Control ◽  
Ubiquitin Ligase ◽  
Essential Role ◽  
E3 Ubiquitin Ligase ◽  
Mitochondrial Quality Control

scholarly journals PINK1: A Bridge between Mitochondria and Parkinson’s Disease

Life ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 371
Author(s):  
Filipa Barroso Gonçalves ◽  
Vanessa Alexandra Morais
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Quality Control ◽  
High Energy ◽  
Common Denominator ◽  
Mitochondrial Quality Control ◽  
Mitochondrial Homeostasis ◽  
Cellular Environment ◽  
Familial Form ◽  
Mitochondrial Functions

Mitochondria are known as highly dynamic organelles essential for energy production. Intriguingly, in the recent years, mitochondria have revealed the ability to maintain cell homeostasis and ultimately regulate cell fate. This regulation is achieved by evoking mitochondrial quality control pathways that are capable of sensing the overall status of the cellular environment. In a first instance, actions to maintain a robust pool of mitochondria take place; however, if unsuccessful, measures that lead to overall cell death occur. One of the central key players of these mitochondrial quality control pathways is PINK1 (PTEN-induce putative kinase), a mitochondrial targeted kinase. PINK1 is known to interact with several substrates to regulate mitochondrial functions, and not only is responsible for triggering mitochondrial clearance via mitophagy, but also participates in maintenance of mitochondrial functions and homeostasis, under healthy conditions. Moreover, PINK1 has been associated with the familial form of Parkinson’s disease (PD). Growing evidence has strongly linked mitochondrial homeostasis to the central nervous system (CNS), a system that is replenished with high energy demanding long-lasting neuronal cells. Moreover, sporadic cases of PD have also revealed mitochondrial impairments. Thus, one could speculate that mitochondrial homeostasis is the common denominator in these two forms of the disease, and PINK1 may play a central role in maintaining mitochondrial homeostasis. In this review, we will discuss the role of PINK1 in the mitochondrial physiology and scrutinize its role in the cascade of PD pathology.

scholarly journals The Landscape of Parkin Variants Reveals Pathogenic Mechanisms and Therapeutic Targets in Parkinson’s Disease

2018 ◽  
Author(s):  
Wei Yi ◽  
Emma J. MacDougall ◽  
Matthew Y. Tang ◽  
Andrea I. Krahn ◽  
Ziv Gan-Or ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Specific Drug ◽  
Common Cause ◽  
Naturally Occurring ◽  
Population Databases ◽  
Early Onset Parkinson’S Disease

AbstractMutations in Parkin (PARK2), which encodes an E3 ubiquitin ligase implicated in mitophagy, are the most common cause of early onset Parkinson’s Disease (PD). Hundreds of naturally occurring Parkin variants have been reported, both in PD patient and population databases. However, the effects of the majority of these variants on the function of Parkin and in PD pathogenesis remains unknown. Here we develop a framework for classification of the pathogenicity of Parkin variants based on the integration of clinical and functional evidence – including measures of mitophagy and protein stability, and predictive structural modeling – and assess 51 naturally occurring Parkin variants accordingly. Surprisingly, only a minority of Parkin variants, even among those previously associated with PD, disrupted Parkin function. Moreover, a few of these naturally occurring Parkin variants actually enhanced mitophagy. Interestingly, impaired mitophagy in several of the most common pathogenic Parkin variants could be rescued both by naturally-occurring (p.V224A) and structure-guided designer (p.W403A; p.F146A) hyperactive Parkin variants. Together, the findings provide a coherent framework to classify Parkin variants based on pathogenicity and suggest that several pathogenic Parkin variants represent promising targets to stratify patients for genotype-specific drug design.

scholarly journals PINK1, Parkin, and Mitochondrial Quality Control: What can we Learn about Parkinson’s Disease Pathobiology?

2017 ◽  
Vol 7 (1) ◽  
pp. 13-29 ◽  
Author(s):  
Dominika Truban ◽  
Xu Hou ◽  
Thomas R. Caulfield ◽  
Fabienne C. Fiesel ◽  
Wolfdieter Springer
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Quality Control ◽  
Mitochondrial Quality Control

The FBXO7 homologue nutcracker and binding partner PI31 in Drosophila melanogaster models of Parkinson’s disease

Genome ◽  
2017 ◽  
Vol 60 (1) ◽  
pp. 46-54 ◽  
Author(s):  
Eric M. Merzetti ◽  
Lindsay A. Dolomount ◽  
Brian E. Staveley
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drosophila Melanogaster ◽  
Ubiquitin Ligase ◽  
E3 Ubiquitin Ligase ◽  
Severe Form ◽  
Altered Expression ◽  
Binding Partner ◽  
Locomotor Control ◽  
Dependent Model

Parkinsonian-pyramidal syndrome (PPS) is an early onset form of Parkinson’s disease (PD) that shows degeneration of the extrapyramidal region of the brain to result in a severe form of PD. The toxic protein build-up has been implicated in the onset of PPS. Protein removal is mediated by an intracellular proteasome complex: an E3 ubiquitin ligase, the targeting component, is essential for function. FBXO7 encodes the F-box component of the SCF E3 ubiquitin ligase linked to familial forms of PPS. The Drosophila melanogaster homologue nutcracker (ntc) and a binding partner, PI31, have been shown to be active in proteasome function. We show that altered expression of either ntc or PI31 in dopaminergic neurons leads to a decrease in longevity and locomotor ability, phenotypes both associated with models of PD. Furthermore, expression of ntc-RNAi in an established α-synuclein-dependent model of PD rescues the phenotypes of diminished longevity and locomotor control.

scholarly journals P1-200: THE ASSOCIATION BETWEEN VITAMIN D AND THE EXPRESSION OF MITOCHONDRIAL QUALITY CONTROL GENES PINK1 AND PARKIN IN PARKINSON'S DISEASE PATIENTS

2019 ◽  
Vol 15 ◽  
pp. P313-P313
Author(s):  
Pelin Sordu ◽  
Gençer Genç ◽  
Merve Alaylıoğlu ◽  
Büşra Şengül ◽  
Irem L. Atasoy ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Vitamin D ◽  
Parkinson's Disease ◽  
Quality Control ◽  
Mitochondrial Quality Control
Sign in / Sign up

Export Citation Format

Share Document