A Rab5 endosomal pathway mediates Parkin-dependent mitochondrial clearance

Damaged mitochondria pose a lethal threat to cells that necessitates their prompt removal. The currently recognized mechanism for disposal of mitochondria is autophagy, where damaged organelles are marked for disposal via ubiquitylation by Parkin. Here we report a novel pathway for mitochondrial elimination, in which these organelles undergo Parkin-dependent sequestration into Rab5-positive early endosomes via the ESCRT machinery. Following maturation, these endosomes deliver mitochondria to lysosomes for degradation. Although this endosomal pathway is activated by stressors that also activate mitochondrial autophagy, endosomal-mediated mitochondrial clearance is initiated before autophagy. The autophagy protein Beclin1 regulates activation of Rab5 and endosomal-mediated degradation of mitochondria, suggesting cross-talk between these two pathways. Abrogation of Rab5 function and the endosomal pathway results in the accumulation of stressed mitochondria and increases susceptibility to cell death in embryonic fibroblasts and cardiac myocytes. These data reveal a new mechanism for mitochondrial quality control mediated by Rab5 and early endosomes

Investigation of mechanical properties of stress-relieved and electron-irradiated tungsten after hydrogen charging

The effect of hydrogen on the hardness and tensile properties of pure tungsten was examined using Vickers hardness and tensile tests. Samples were exposed to high-pressure hydrogen gas (5.8 MPa). The tensile behavior, tensile fracture surface, and hardness of as-received and stress-relieved tungsten did not change after hydrogen charging, owing to the low solubility of hydrogen. Therefore, to understand the effect of hydrogen on these materials, experiments must be performed to trap more hydrogen atoms at dislocations. In contrast, the hardness of electron-irradiated tungsten increased after hydrogen charging. Additionally, after a heat treatment at 473 K, hydrogen atoms dissociated from single vacancies, and the hardness decreased to the pre-charged value. Thus, single vacancies decorated with hydrogen atoms are expected to obstruct dislocation motion. Keywords: Tungsten, Hydrogen, Hardness, Tensile test, Defects, Electron irradiatio