Confocal microscopy showing the inside of a human cell with damaged lysosomes (magenta stained circles) and calponin 2 around the damaged lysosomes (light blue shape around it). The nucleus of the cell is visible as a dark blue semicircle. Credit: Dr. Bojana Kravic
Billions of cells in our body work non-stop to keep us alive. This generates waste that decomposes into specialized cell organs. But what if cell bins don’t work? Researchers assume that this is the cause of numerous diseases. Biologists at the University of Duisburg-Essen (UDE), along with a team from Munich, have now been able to show how cells are protected from their defective containers, because their contents are quite serious.
Like the organs of the human body, cells also have specialized structures inside them called organelles. These include lysosomes, cell debris containers. Not only do they break down the waste produced in the cell, but they also break down invasive pathogens such as bacteria. To this end, the small spheres are equipped with an acidic interior and a large number of enzymes. They are surrounded by a membrane that traps the dangerous mixture inside.
If this membrane is damaged, the mixture is poured into the cell itself and, in the worst case, leads to cell death. As a safety measure against the threat of the interior, the cells have developed the following mechanism: they surround the perforated lysosome with another membrane intact and transport it to another lysosome as in a bag to degrade.
In collaboration with a team from the Ludwig-Maximilians-Universität Munich, researchers in the group led by Professor Hemmo Meyer of the UDE were able to show that this degradation process depends on several factors: calponin 2 protein helps to form a new envelope around the damaged lysosome. Subsequently, it must be removed quickly. Therefore, it is marked with the small ubiquitin molecule as a package with an address label. The enzyme p97 reads this label and then removes calponin 2. If this process is damaged at some point, a damaged lysosome cannot be degraded and eventually leads to cell death.
An interrupted process could play a role in the development of various diseases such as tumors, inflammation, neurodegenerative disorders, and cardiovascular disease. “Our findings help to understand the processes involved in the development and progression of diseases,” explains the first author, Dr. Bojana Kravic. “Effective therapeutic approaches can only be developed if we know these pathways.”
The study is published in Molecular Cell.
Researchers reveal a new molecular mechanism for the risk of Parkinson’s disease. More information: Bojana Kravić et al, The ubiquitin profile of lysophagy identifies the CNN2 actin stabilizer as a target of VCP / p97 and discovers a link to HSPB1, Molecular Cell (2022). DOI: 10.1016 / j.molcel.2022.06.012
Provided by the University of Duisburg-Essen
Citation: Catabolic processes in cells: Controlling the danger inside (2022, July 6) retrieved July 7, 2022 from
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