778 – Ncx1/Ca Signal Pathway Contributes to the Autophagy Regulation During TGF-Β Induced Hepatic Stellate Cell Activation
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Autophagy is an evolutionarily conserved biological phenomenon related to protein degradation and organelle turnover. Three types of autophagy have been defined: macroautophagy, microautophagy, and chaperone-mediated autophagy, which differ the way of in the delivery of substrates to the lysosome. In macroautophagy, substrates are wrapped in a double membrane structure, called the autophagosome. The formation of the autophagosome and its fusion with the lysosome are genetically controlled by a series of autophagy molecules and are activated in response to a number of environmental cues. Much has yet to be learned about the signaling pathway and the molecular mechanisms about this process. Autophagy is important to multiple cellular functions, particularly for nutrient and energy balance, and the turnover of cellular substances. The relationship of autophagy with cell death is complicated and may be context-dependent. Whereas the nature of autophagic death has yet to be carefully defined, it seems that autophagy may, in fact, be a key regulator of both apoptosis and necrosis. In this context, the roles of macroautophagy in both prosurvival and prodeath have been identified. Understanding the circumstance in which autophagy affects cell functions and therefore cell viability is critical for the future intervention of this process to control cancer, tissue injury, and other disease processes.
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Bcl-2 family proteins are known to regulate mitochondrial integrity and apoptosis. More recently, they have been found to play a role in regulating autophagy. Autophagy is a process involved in removing excess or damaged organelles. Bnip3 is a pro-apoptotic BH3-only protein which is known to cause mitochondrial dysfunction and cell death. Bnip3 is also a potent inducer of mitochondrial autophagy. In this study I have investigated the mechanism by which Bnip3 promotes removal of mitochondria via autophagy. Bnip3 contains a C-terminal transmembrane (TM) domain that is essential for homodimerization and pro- apoptotic function. Here, I show that Bnip3 homodimerization is also a requirement for induction of autophagy. Mutations in Bnip3 that disrupt homodimerization, but do not interfere with mitochondrial localization, failed to induce autophagy. In addition, I found that endogenous Bnip3 was localized to both the mitochondria and the endoplasmic reticulum (ER) in HeLa cells. To investigate the effects of Bnip3 at ER on autophagy, Bnip3 was targeted specifically to mitochondria or ER by substituting the Bnip3 TM domain with that of Acta or cytochromeb5, respectively. Interestingly, Bnip3 induced significant autophagy in cells from both sites. Moreover, Bnip3 induced removal of mitochondria and ER by autophagy via binding to LC3 on the autophagosome. Ablation of the Bnip3-LC3 interaction had no effect on the induction of general autophagy but significantly reduced autophagy of mitochondria and ER. Thus, our data suggest that the Bnip3 homodimer functions as an autophagy receptor to ensure removal of mitochondria and ER
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A A A A AA A A A A A A A A AA A A A A A A A A A A A AA A A A A A A A A A A A A A A A A A A A AA A A A A A A A A A A A A A A A A A AA A A A A A A A A A A A A A A A A A A A A A A A A A A A AA A A A A A A A A A A A A A A A A A A A A A A A AA A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A AA A A A A A A A A A A A A A A A A A A A A A A A A A A A A A AA A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A
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Autophagy is an evolutionarily conserved cellular catabolic pathway in response to metabolic stresses.Autophagy is activated with the formation of double-membrane structures named autophagosome,which can ferry cytoplasmic impaired organelles and proteins to the lysosome for degradation.Autophagy is regarded as a quality control mechanism that contributes to the maintainance of cell homeostasis.By far,the core proteins involved in the classical autophagy pathway have been identified.The activity and function of these proteins in autophagy flux following stress signal inputs is being investigated.We reviewed recent studies about the regulation of autophagy-related proteins with posttranslational modifications under conditions of metabolic stresses,in order to help the further understanding of autophagy.
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The nationally-recognized Susquehanna
Chorale will delight audiences of all
ages with a diverse mix of classic and
contemporary pieces. The ChoraleAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂA¢AÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂs
performances have been described
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music making, successful in their
aim to make the audience feel,
to be moved, to be part of the
performance - and all this while
working at an extremely high
musical level.AÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂA¢AÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂAÂA Experience choral
singing that will take you to new
heights!
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