PINK1-Dependent mitophagy inhibits elevated ubiquitin phosphorylation caused by mitochondrial damage

Ubiquitin phosphorylation by the mitochondrial protein kinase PTEN-induced kinase 1 (PINK1), upon mitochondrial depolarization, is an important intermediate step in the recycling of damaged mitochondria via mitophagy. As mutations in PINK1 can cause early-onset Parkinson’s disease (PD), there has been a growing interest in small-molecule activators of PINK1-mediated mitophagy as potential PD treatments. Herein, we show that N6-substituted adenosines, such as N6-(2-furanylmethyl)adenosine (known as kinetin riboside) and N6-benzyladenosine, activate PINK1 in HeLa cells and induce PINK1-dependent mitophagy in primary mouse fibroblasts. Interestingly, pre-treatment of HeLa cells and astrocytes with these compounds inhibited elevated ubiquitin phosphorylation that is induced by established mitochondrial depolarizing agents, carbonyl cyanide m-chlorophenyl-hydrazine and niclosamide. Together, this highlights N6-substituted adenosines as progenitor PINK1 activators that could potentially be developed, in the future, as treatments for aged and sporadic PD patients who have elevated phosphorylated ubiquitin levels in the brain

Fabrication of MIS photodetector with Ge nanocrystals grown by MBE

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Comparison of ZnO thin films on different substrates obtained by sol-gel process and deposited by spin-coating technique

521-529In the present paper, zinc oxide thin films obtained by sol gel process and deposited on glass, sapphire, Si (100), Si (111) and ZnO substrates by spin-coating technique have been studied. Effects of using different substrates on the structural, morphological and optical properties have been investigated. The structural properties have been analyzed using X-ray diffraction (XRD) and the recorded patterns indicated that all the deposited films are polycrystalline with a hexagonal Wurtzite structure and exhibit preferentially oriented along the c-axis direction. The surface morphology has been examined by Scanning Electron Microscopy which revealed that the microstructure of the films strongly affected by the nature and orientation of substrate namely grain shape and size. Optical absorbance measurements have been taken using UV-Vis spectrophotometer and the calculated values of the direct band gap energy are around 3, 3.08 and 3.19 eV, for the ZnO films deposited on ZnO, sapphire c and glass substrates, respectively. Photoluminescence measurements taken at 4 K exhibit a near band edge composed by two principal’s peaks situated at 3.36 and 3.31 eV and attributed to the neutral donor bound exciton (D°X) and to the deep acceptor (A°X), their intensity varied with the nature of substrate