N-degron-mediated degradation and regulation of mitochondrial PINK1 kinase.

Current Genetics
Mohamed A Eldeeb, Mohamed A Ragheb

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative condition characterized by a gradual loss of a specific group of dopaminergic neurons in the substantia nigra. Importantly, current treatments only address the symptoms of PD, yet not the underlying molecular causes. Concomitantly, the function of genes that cause inherited forms of PD point to mitochondrial dysfunction as a major contributor in the etiology of PD. An inherent challenge that mitochondria face is the continuous exposure to diverse stresses including high levels of reactive oxygen species and protein misfolding, which increase their likelihood of dysregulation. In response, eukaryotic cells have evolved sophisticated quality control mechanisms to identify, repair and/or eliminate abnormal dysfunctional mitochondria. One such mechanism is mitophagy, a process which involves PTEN-induced putative kinase 1 (PINK1), a mitochondrial Ser/Thr kinase and Parkin, an E3 ubiquitin ligase, each encoded by genes responsible for early-onset autosomal recessive familial PD. Over 100 loss-of-function mutations in the PTEN-induced putative kinase 1 (PINK1) gene have been reported to cause autosomal recessive early-onset PD. PINK1 acts upstream of Parkin and is essential ...Continue Reading

References

Apr 17, 2004·Science·Enza Maria ValenteNicholas W Wood
Aug 2, 2005·Molecular and Cellular Biology·Takafumi TasakiYong Tae Kwon
Oct 2, 2007·Nature Cell Biology·Hélène Plun-FavreauJulian Downward
Aug 19, 2008·The Journal of Biological Chemistry·Alexander Varshavsky
Nov 26, 2008·The Journal of Cell Biology·Derek NarendraRichard J Youle
Jan 30, 2010·Science·Cheol-Sang HwangAlexander Varshavsky
Dec 1, 2010·The Journal of Cell Biology·Seok Min JinRichard J Youle
Dec 2, 2010·Molecular Neurobiology·Inês Pimenta de CastroSamantha Hui Yong Loh
May 28, 2011·Journal of Neurochemistry·Liliane GlauserDarren J Moore
Jun 3, 2011·Protein Science : a Publication of the Protein Society·Alexander Varshavsky
Jun 7, 2011·Annual Review of Genomics and Human Genetics·Ian MartinTed M Dawson
Sep 1, 2011·Biochimica Et Biophysica Acta·Dario C AltieriLucia R Languino
Apr 25, 2012·Annual Review of Biochemistry·Takafumi TasakiYong Tae Kwon
May 15, 2012·Human Mutation·Marc CrutsChristine Van Broeckhoven
Oct 15, 2013·Autophagy·Koji Yamano, Richard J Youle
Nov 6, 2013·The Journal of Biological Chemistry·Kei OkatsuNoriyuki Matsuda
Feb 25, 2014·Cell Metabolism·Angelika B HarbauerChris Meisinger
Apr 23, 2014·The Journal of Cell Biology·Lesley A KaneRichard J Youle
May 3, 2014·Nature·Fumika KoyanoNoriyuki Matsuda
May 31, 2014·Trends in Cell Biology·Daniel J GibbsMichael J Holdsworth
Aug 12, 2014·The EMBO Journal·Ayumu SugiuraHeidi M McBride
Jan 23, 2015·Neuron·Alicia M Pickrell, Richard J Youle
Jan 9, 2016·Protein and Peptide Letters·Mohamed Eldeeb, Richard Fahlman
Apr 12, 2016·Current Opinion in Cell Biology·Martin van der LaanNikolaus Pfanner
Jun 3, 2016·Journal of Neurochemistry·Aaron VoigtKonstanze F Winklhofer
Sep 8, 2016·The Journal of Biological Chemistry·Mohamed A Eldeeb, Richard P Fahlman
Jan 28, 2017·Science·Shun-Jia ChenAlexander Varshavsky
Mar 17, 2017·Annual Review of Biochemistry·Nils Wiedemann, Nikolaus Pfanner
May 2, 2017·Annual Review of Biochemistry·Ivan Dikic

❮ Previous
Next ❯

Citations

Oct 2, 2020·International Journal of Molecular Sciences·Fang LuoXin Wang
Oct 18, 2020·Biomedicines·Maria EjmaGjumrakch Aliev
Aug 8, 2021·International Journal of Molecular Sciences·Jung Gi KimHyunjoo Cha-Molstad

❮ Previous
Next ❯

Methods Mentioned

BETA
ubiquitination
acetylation
GTPase

Related Concepts

Related Feeds

Parkinson's Disease & Autophagy

Autophagy leads to degradation of damaged proteins and organelles by the lysosome. Impaired autophagy has been implicated in several diseases. Here is the role of autophagy in Parkinson’s disease.

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

Parkinson's Disease & Autophagy (MDS)

Autophagy leads to degradation of damaged proteins and organelles by the lysosome. Impaired autophagy has been implicated in several diseases. Here is the role of autophagy in Parkinson’s disease.

Autophagy Networks

Autophagy is a lysosomal pathway that involves degradation of proteins and functions in normal growth and pathological conditions, through a series of complex networks. The catabolic process involves delivery of proteins and organelles to the lysosome. Here is the latest research on autophagy networks.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms