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.
Parkin and PINK1: much more than mitophagy.
Baltimore, United States. In Trends Neurosci, Jun 2014
In support of this theory, data from multiple PD models have linked Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and parkin, two recessive PD genes, in a common pathway impacting mitochondrial health, prompting a flurry of research to identify their mitochondrial targets.
Parkinson's disease-implicated kinases in the brain; insights into disease pathogenesis.
Australia. In Front Mol Neurosci, Dec 2013
Elevated phosphorylation of the PD-defining pathological protein, α-synuclein, correlates with its aggregation and toxic accumulation in neurons, whilst genetic missense mutations in the kinases PTEN-induced putative kinase 1 and leucine-rich repeat kinase 2, increase susceptibility to PD. Experimental evidence also links kinases of the phosphoinositide 3-kinase and mitogen-activated protein kinase signaling pathways, amongst others, to PD. Understanding how the levels or activities of these enzymes or their substrates change in brain tissue in relation to pathological states can provide insight into disease pathogenesis.
Emerging modes of PINK1 signaling: another task for MARK2.
Hamburg, Germany. In Front Mol Neurosci, Dec 2013
PTEN-induced kinase 1 (PINK1) acts at multiple levels to promote mitochondrial health, including regulatory influence on ATP-synthesis, protein quality control, apoptosis, mitochondrial transport, and destiny.