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Studies performed in the liver in the 1960s led to the identification of lysosomes and the discovery of autophagy, the process by which intracellular proteins and organelles are degraded in lysosomes. Early studies in hepatocytes also uncovered how nutritional status regulates autophagy and how various circulating hormones modulate the activity of this(More)
The activity of chaperone-mediated autophagy (CMA), a catabolic pathway for selective degradation of cytosolic proteins in lysosomes, decreases with age, but the consequences of this functional decline in vivo remain unknown. In this work, we have generated a conditional knockout mouse to selectively block CMA in liver. We have found that blockage of CMA(More)
Keratin intermediate filaments (KIFs) form a fibrous polymer network that helps epithelial cells withstand external mechanical forces. Recently, we established a correlation between the structure of the KIF network and its local mechanical properties in alveolar epithelial cells. Shear stress applied across the cell surface resulted in the structural(More)
Malfunction of autophagy, the process that mediates breakdown and recycling of intracellular components in lysosomes, has been linked to a variety of human diseases. As the number of pathologies associated with defective autophagy increases, emphasis has switched from the mere description of the status of autophagy in these conditions to a more mechanistic(More)
Chaperone-mediated autophagy (CMA), a cellular process that contributes to protein quality control through targeting of a subset of cytosolic proteins to lysosomes for degradation, undergoes a functional decline with age. We have used a mouse model with liver-specific defective CMA to identify changes in proteostasis attributable to reduced CMA activity in(More)
The importance of cellular quality-control systems in the maintenance of neuronal homoeostasis and in the defence against neurodegeneration is well recognized. Chaperones and proteolytic systems, the main components of these cellular surveillance mechanisms, are key in the fight against the proteotoxicity that is often associated with severe(More)
Autophagy, the process of degrading intracellular components in lysosomes, plays an important role in the central nervous system by contributing to neuronal homeostasis. Autophagic failure has been linked to neurologic dysfunction and a variety of neurodegenerative diseases. Recent investigation has revealed a novel role for autophagy in the context of(More)
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