Mitochondrial dynamics and mitophagy in Parkinson's disease: A fly point of view.
Venice, Italy. In Neurobiol Dis, 06 Dec 2015
In recent years the fruit fly Drosophila melanogaster has proved to be a valuable model system to evaluate the consequences of mitochondria quality control dysfunction in vivo, particularly with respect to PINK1/Parkin dependent dysregulation of mitophagy in the onset of Parkinson's Disease (PD).
Parkinson's disease proteins: Novel mitochondrial targets for cardioprotection.
London, United Kingdom. In Pharmacol Ther, 16 Nov 2015
In dopaminergic neurons of the substantial nigra, these PD proteins, which include Parkin, PINK1, DJ-1, LRRK2, and α-synuclein, play essential roles in preventing cell death - through maintaining normal mitochondrial function, protecting against oxidative stress, mediating mitophagy, and preventing apoptosis.
Animal models of Parkinson's disease: An updated overview.
Marseille, France. In Rev Neurol (paris), 03 Oct 2015
"Classic" models are based on neurotoxins that selectively target catecholaminergic neurons (such as 6-hydroxydopamine, 1-methyl-1,2,3,6-tetrahydropiridine, agricultural pesticides, etc.), while more recent models employ genetic manipulations that either introduce mutations similar to those find in familial cases of PD (α-synuclein, DJ-1, PINK1, Parkin, etc.) or selectively disrupt nigrostriatal neurons (MitoPark, Pitx3, Nurr1, etc.).
Expanding the ubiquitin code through post-translational modification.
Frankfurt am Main, Germany. In Embo Rep, Sep 2015
In mammals, the PINK1 kinase activates ubiquitin ligase Parkin by phosphorylating S65 of Ub and of the Parkin Ubl domain, which in turn promotes the amplification of autophagy signals necessary for the removal of damaged mitochondria.
Mechanism of phospho-ubiquitin-induced PARKIN activation.
Cambridge, United Kingdom. In Nature, Sep 2015
The E3 ubiquitin ligase PARKIN (encoded by PARK2) and the protein kinase PINK1 (encoded by PARK6) are mutated in autosomal-recessive juvenile Parkinsonism (AR-JP) and work together in the disposal of damaged mitochondria by mitophagy.
Expression of Neuronal and Signaling Proteins in Penumbra around a Photothrombotic Infarction Core in Rat Cerebral Cortex.
Rostov-na-Donu, Russia. In Biochemistry (mosc), Jun 2015
The observed upregulation of penumbra proteins involved in maintaining neurite integrity and guidance (NAV3, MAP1, CRMP2, PMP22); intercellular interactions (N-cadherin); synaptic transmission (glutamate decarboxylase, tryptophan hydroxylase, Munc-18-1, Munc-18-3, and synphilin-1); mitochondria quality control and mitophagy (PINK1 and Parkin); ubiquitin-mediated proteolysis and tissue clearance (UCHL1, PINK1, Parkin, synphilin-1); and signaling proteins (PKBα and ERK5) could be associated with tissue recovery.
How mitochondrial dynamism orchestrates mitophagy.
Beersheba, Israel. In Circ Res, Jun 2015
Here, we review accumulating evidence supporting important roles for mitochondrial fission and fusion in cardiac mitochondrial quality control, focusing on the PTEN-induced putative kinase 1-Parkin mitophagy pathway.
Quantifying ubiquitin signaling.
Boston, United States. In Mol Cell, Jun 2015
Here, we review how quantitative proteomic tools and enrichment strategies are being used to quantify UB-dependent signaling systems, and to integrate UB signaling with regulatory phosphorylation events, illustrated with the PINK1/PARKIN pathway.
The mitochondrial deubiquitinase USP30 opposes parkin-mediated mitophagy.
San Francisco, United States. In Nature, Jul 2014
Here we report that USP30, a deubiquitinase localized to mitochondria, antagonizes mitophagy driven by the ubiquitin ligase parkin (also known as PARK2) and protein kinase PINK1, which are encoded by two genes associated with Parkinson's disease.