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söndag 19 maj 2019

Artikkeleita ubikitiini ja mitokondria

Best matches for ubiquitin and mitochondria:

(2016 uutta tietoa mitokondria ubikitiiniproteosomi järjestelmästä(UPS))

On the linkage between the ubiquitin-proteasome system and the mitochondria. Lehmann G et al. Biochem Biophys Res Commun. (2016)
Several metabolic pathways critical for cellular homeostasis occur in the mitochondria. Because of the evolution of mitochondria and their physical separation, these pathways have traditionally been thought to be free from regulation by the ubiquitin-proteasome system. This perception has recently been challenged by evidence for the presence of ubiquitin system components in the mitochondria.
Furthermore, it has been shown that certain mitochondrial proteins are conjugated by ubiquitin, and some of them are degraded by the proteasome. Of particular interest is the finding that some of these proteins are localized to the inner membrane and matrix, which rules out that their targeting is mediated by the cytosolic ubiquitin system.
However, the extent of the involvement of the ubiquitin system in mitochondrial regulation is not known.
The present study addresses this surprising finding, employing several independent approaches.

First, we identified reported ubiquitin conjugates in human and yeast mitochondria and
found that a large fraction of the mitochondrial proteome (62% in human) is ubiquitinated, with most proteins localized to the inner membrane and matrix.
Next, we searched the literature and found that numerous ubiquitin system components localize to the mitochondria and/or contain mitochondrial targeting sequences.
Finally, we identified reported protein-protein interactions between ubiquitin system components and mitochondrial proteins.

These unexpected findings suggest that mitochondrial regulation by the ubiquitin system is fundamental and may have broad biomedical implications.

2017 ( Mitokondria , ubikitiiniproteosomisysteemi UPS , pestisidit ja PD)

Effects of Commonly Used Pesticides in China on the Mitochondria and Ubiquitin-Proteasome System in Parkinson's Disease. Chen T et al. Int J Mol Sci. (2017) Abstract

Evidence continues to accumulate that pesticides are the leading candidates of environmental toxins that may contribute to the pathogenesis of Parkinson's disease. The mechanisms, however, remain largely unclear. According to epidemiological studies, we selected nine representative pesticides (paraquat, rotenone, chlorpyrifos, pendimethalin, endosulfan, fenpyroximate, tebufenpyrad, trichlorphon and carbaryl) which are commonly used in China and detected the effects of the pesticides on mitochondria and ubiquitin-proteasome system (UPS) function.
Our results reveal that all the nine studied pesticides induce morphological changes of mitochondria at low concentrations. Paraquat, rotenone, chlorpyrifos, pendimethalin, endosulfan, fenpyroximate and tebufenpyrad induced mitochondria fragmentation. Furthermore, some of them (paraquat, rotenone, chlorpyrifos, fenpyroximate and tebufenpyrad) caused a significant dose-dependent decrease of intracellular ATP. Interestingly, these pesticides which induce mitochondria dysfunction also inhibit 26S and 20S proteasome activity. However, two out of the nine pesticides, namely trichlorphon and carbaryl, were found not to cause mitochondrial fragmentation or functional damage, nor inhibit the activity of the proteasome, which provides significant guidance for selection of pesticides in China.
Moreover, our results demonstrate a potential link between inhibition of mitochondria and the UPS, and pesticide-induced Parkinsonism.

2015 (Mitofagiaa ja mitokondriahomeostaasia säätelee RBR-E3-ligaasi PRKN ja mitokondriaalinen deunikitinaasi DUB USP30).

USP30 and parkin homeostatically regulate atypical ubiquitin chains on mitochondria. Cunningham CN et al. Nat Cell Biol. (2015) Multiple lines of evidence indicate that mitochondrial dysfunction is central to Parkinson's disease. Here we investigate the mechanism by which parkin, an E3 ubiquitin ligase (PRKN, RBR- ubiquitin ligase) , and USP30, a mitochondrion-localized deubiquitylase (DUB), regulate mitophagy. We find that mitochondrial damage stimulates parkin to assemble Lys 6, Lys 11 and Lys 63 chains on mitochondria, and that USP30 is a ubiquitin-specific deubiquitylase with a strong preference for cleaving Lys 6- and Lys 11-linked multimers. Using mass spectrometry, we show that recombinant USP30 preferentially removes these linkage types from intact ubiquitylated mitochondria and counteracts parkin-mediated ubiquitin chain formation in cells. These results, combined with a series of chimaera and localization studies, afford insights into the mechanism by which a balance of ubiquitylation and deubiquitylation regulates mitochondrial homeostasis, and suggest a general mechanism for organelle autophagy.

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söndag 19 maj 2019

Artikkeleita ubikitiini ja mitokondria

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