Chaperone-Mediated Autophagy: Tales from an Old "Picky" Broom |
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| Air date: | Wednesday, October 01, 2008, 3:00:00 PM |
| Category: | Wednesday Afternoon Lectures |
| Runtime: | 60 minutes |
| NLM Title: | Chaperone-mediated autophagy : tales from an old "picky" broom [electronic resource] / Ana Maria Cuervo. |
| Series: | NIH director's Wednesday afternoon lecture series |
| Author: | Cuervo, Ana Maria. National Institutes of Health (U.S.) |
| Publisher: | [Bethesda, Md. : National Institutes of Health, 2008] |
| Other Title(s): | NIH director's Wednesday afternoon lecture series |
| Abstract: | (CIT): Cells count on surveillance systems to handle protein alterations. Malfunctioning of these systems contribute in large extend to the abnormal accumulation of those altered proteins in cells and tissues in numerous diseases and in aging. Our studies have focused primarily in one of the cellular systems for protein removal, chaperone-mediated autophagy (CMA), which mediates selective targeting of cytosolic proteins to lysosomes for their degradation. CMA is active in most mammalian cell types but its activity varies depending on cellular conditions. Maximal activation of CMA is attained during stresses such as nutritional stress, mild-oxidative stress or toxin exposure. Degradation by CMA requires the presence of a targeting motif in the substrate protein, a set of cytosolic and lysosomal chaperones and a receptor protein at the lysosomal membrane. Blockage of CMA in culture cells diminishes their ability to adapt to most types of stresses and promotes formation of protein aggregates. Using this model, we have revealed a cross-talk among different removal systems, since in response to diminished CMA activity cells activate other forms of autophagy that compensate for CMA failure, but renders them susceptible to stress. CMA activity declines with age and in some age-related pathologies such as Parkinson"s disease. We have identified the reason for the decline in CMA function with age as a decrease in the levels of the lysosomal receptor that mediates substrate translocation. Our group is currently developing different approaches aimed to restore normal CMA activity in old rodents. These models would help us evaluate the importance of maintaining proper protein removal until advanced ages, and, on light of the observed cross-talk among autophagic pathways, the effect that repairing one autophagic pathway may have on the functioning of the others. The NIH Director's Wednesday Afternoon Lecture Series includes weekly scientific talks by some of the top researchers in the biomedical sciences worldwide. For more information, visit http://www.aecom.yu.edu/cuervo/. |
| Subjects: | Autophagy--physiology Molecular Chaperones |
| Publication Types: | Government Publications Lectures |
| Download: | Download
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| NLM Classification: | QU 375 |
| NLM ID: | 101488617 |
| CIT File ID: | 14680 |
| CIT Live ID: | 7016 |
| Permanent link: | http://videocast.nih.gov/launch.asp?14680 |
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Enhanced Audio Podcast | 59:56 |
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Enhanced Video Podcast | 59:56 | |