We noted you are experiencing viewing problems
-
Check with your IT department that JWPlatform, JWPlayer and Amazon AWS & CloudFront are not being blocked by your network. The relevant domains are *.jwplatform.com, *.jwpsrv.com, *.jwpcdn.com, jwpltx.com, jwpsrv.a.ssl.fastly.net, *.amazonaws.com and *.cloudfront.net. The relevant ports are 80 and 443.
-
Check the following talk links to see which ones work correctly:
Auto Mode
HTTP Progressive Download Send us your results from the above test links at access@hstalks.com and we will contact you with further advice on troubleshooting your viewing problems. -
No luck yet? More tips for troubleshooting viewing issues
-
Contact HST Support access@hstalks.com
-
Please review our troubleshooting guide for tips and advice on resolving your viewing problems.
-
For additional help, please don't hesitate to contact HST support access@hstalks.com
We hope you have enjoyed this limited-length demo
This is a limited length demo talk; you may
login or
review methods of
obtaining more access.
Printable Handouts
Navigable Slide Index
- Introduction
- Lysosome
- Autophagy
- Autophagy is a receptor-mediated process
- mTORC1 is the master regulator of autophagy
- Transcriptional regulation of autophagy
- Autophagy in health and diseases
- Lysosomal storage disorders (LSDs)
- LSD mouse and cellular models
- Lysosomal vacuolization (1)
- Lysosomal vacuolization (2)
- Accumulation of LC3+ vesicles
- Reduced co-localization of Lamp1 with LC3 and P62
- LC3II accumulation is not due to an enhanced AV biogenesis (1)
- LC3II accumulation is not due to an enhanced AV biogenesis (2)
- Accumulation of autophagy substrates
- Reduced co-localization of Lamp1 with LC3
- Reduced co-localization of Lamp1 with p62
- Defective autophagosome degradation, but not biogenesis, in LSD
- LC3-tandem assay to study AV-lysosome fusion
- Proposed model of autophagy dysfunction in LSD
- Can we improve LSD phenotype by rescuing autophagy defects in MPS?
- Development of fluorescent assay to measure AV-lysosome fusion
- mTORC1 inhibitors increase AV-lysosome fusion
- mTORC1 inhibition enhances autophagy substrate degradation
- Genetic approach to inhibit mTORC1
- mTORC1 inhibition enhances AV-lysosome fusion
- mTORC1 inhibition enhances the delivery of autophagy substrates to lysosomes
- mTORC1 inhibition DOES NOT rescue lysosomal storage
- mTORC1 inhibition improves bone growth retardation
- Pharmacological modulation of autophagy rescues autophagy defects
- Pharmacological modulation of autophagy rescues autophagy defects
- Pharmacological modulation of autophagy improves bone growth retardation
- Key conclusions
- Acknowledgements
Topics Covered
- Overview of the lysosome and autophagy
- Lysosomal storage disorders (LSDs)
- Lysosomal vacuolization
- Accumulation of LC3+ vesicles
- Studying co-localization of Lamp1 with LC3 and p62
- LC3-tandem assay to study AV-lysosome fusion
- mTORC1 inhibitors and AV-lysosome fusion
- Pharmacological modulation of autophagy
Talk Citation
Settembre, C. (2019, November 28). Autophagy dysfunction in lysosomal storage disorders [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 9, 2024, from https://doi.org/10.69645/DFAL2334.Export Citation (RIS)
Publication History
Financial Disclosures
- There are no commercial/financial matters to disclose.
Other Talks in the Series: Autophagy and Lysosomal Storage Diseases
Transcript
Please wait while the transcript is being prepared...
0:00
Good morning. My name is Carmine Settembre.
I'm a group leader at the Telethon Institute of Genetics and Medicine in Naples,
Italy, and also associate professor of
medical genetics at the University of Naples Federico II.
Today, I'm going to talk to you about evidences suggesting that
autophagy dysfnction is one of
the main pathogenic mechanism in lysosomal storage disorders.
0:28
So the lysosome is the main catabolic organelle of the cells because it's
able to digest virtually any biological substrates within its lumen.
This digestion is possible thanks to the presence of several lysosomal hydrolases,
which are enzymes that are able to digest virtually any biological substrates,
in a more simple units,
within the lumen of the lysosome.
Cellular substrates are delivered to the lysosome mainly through independent pathway.
Extracellular substrates are delivered to the lysosome via endocytosis,
while intracellular substrates are delivered to the lysosome via autophagy.
1:14
The process of autophagy starts with
the biogenesis of double membrane vesicles known as autophagosome.
This double membrane vesicle recognize
intracellular material that needs to be degraded by lysosome.
So then this material is basically sequestered within this double membrane vesicles,
and then delivered to the lysosome upon autophagosome lysosome fusion.
Once this material is delivered within the lysosome,
lysosome hydrolases digest this material in more simple units
such as amino acids from proteins or fatty acids from complex lipids and so on,
and then this digested material is recycled
back within the cytoplasm and then can be reused by the cells,
either to generate energy during period of cell fusion or as
a building block for the biosynthesis of new complex molecules.