TY - JOUR
T1 - PINK1, Parkin, and Mitochondrial Quality Control
T2 - What can we Learn about Parkinson's Disease Pathobiology?
AU - Truban, Dominika
AU - Hou, Xu
AU - Caulfield, Thomas R.
AU - Fiesel, Fabienne C.
AU - Springer, Wolfdieter
N1 - Funding Information:
W.S. is partially supported by the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) [R01 #NS085070], the Michael J. Fox Foundation for Parkinson's Research and the Foundation for Mitochondrial Medicine, the Mayo Clinic Center for Regenerative Medicine (CRM), Center for Individualized Medicine (CIM), and Center for Biomedical Discovery (CBD), the Marriott Family Foundation, and a Gerstner Family Career Development Award. F.C.F. is supported by the American Parkinson Disease Association (APDA) and the Younkin Scholar Program.
Publisher Copyright:
© 2017 - IOS Press and the authors. All rights reserved.
PY - 2017
Y1 - 2017
N2 - The first clinical description of Parkinson's disease (PD) will embrace its two century anniversary in 2017. For the past 30 years, mitochondrial dysfunction has been hypothesized to play a central role in the pathobiology of this devastating neurodegenerative disease. The identifications of mutations in genes encoding PINK1 (PTEN-induced kinase 1) and Parkin (E3 ubiquitin ligase) in familial PD and their functional association with mitochondrial quality control provided further support to this hypothesis. Recent research focused mainly on their key involvement in the clearance of damaged mitochondria, a process known as mitophagy. It has become evident that there are many other aspects of this complex regulated, multifaceted pathway that provides neuroprotection. As such, numerous additional factors that impact PINK1/Parkin have already been identified including genes involved in other forms of PD. A great pathogenic overlap amongst different forms of familial, environmental and even sporadic disease is emerging that potentially converges at the level of mitochondrial quality control. Tremendous efforts now seek to further detail the roles and exploit PINK1 and Parkin, their upstream regulators and downstream signaling pathways for future translation. This review summarizes the latest findings on PINK1/Parkin-directed mitochondrial quality control, its integration and cross-talk with other disease factors and pathways as well as the implications for idiopathic PD. In addition, we highlight novel avenues for the development of biomarkers and disease-modifying therapies that are based on a detailed understanding of the PINK1/Parkin pathway.
AB - The first clinical description of Parkinson's disease (PD) will embrace its two century anniversary in 2017. For the past 30 years, mitochondrial dysfunction has been hypothesized to play a central role in the pathobiology of this devastating neurodegenerative disease. The identifications of mutations in genes encoding PINK1 (PTEN-induced kinase 1) and Parkin (E3 ubiquitin ligase) in familial PD and their functional association with mitochondrial quality control provided further support to this hypothesis. Recent research focused mainly on their key involvement in the clearance of damaged mitochondria, a process known as mitophagy. It has become evident that there are many other aspects of this complex regulated, multifaceted pathway that provides neuroprotection. As such, numerous additional factors that impact PINK1/Parkin have already been identified including genes involved in other forms of PD. A great pathogenic overlap amongst different forms of familial, environmental and even sporadic disease is emerging that potentially converges at the level of mitochondrial quality control. Tremendous efforts now seek to further detail the roles and exploit PINK1 and Parkin, their upstream regulators and downstream signaling pathways for future translation. This review summarizes the latest findings on PINK1/Parkin-directed mitochondrial quality control, its integration and cross-talk with other disease factors and pathways as well as the implications for idiopathic PD. In addition, we highlight novel avenues for the development of biomarkers and disease-modifying therapies that are based on a detailed understanding of the PINK1/Parkin pathway.
KW - PINK1
KW - Parkin
KW - Parkinson's disease
KW - mitochondria
KW - mitophagy
KW - ubiquitin
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U2 - 10.3233/JPD-160989
DO - 10.3233/JPD-160989
M3 - Review article
C2 - 27911343
AN - SCOPUS:85012213619
SN - 1877-7171
VL - 7
SP - 13
EP - 29
JO - Journal of Parkinson's disease
JF - Journal of Parkinson's disease
IS - 1
ER -