Aug
07

Post #8: Aggre…what?

Aggrephagy! It’s the connection I’ve been looking for!

Hi everyone! It is hard to believe that the end of this summer is rapidly approaching. However, I am very happy with all the progress I made on my thesis over the course of these past 10 weeks. Even though I am done with bench work for the summer, I still wanted to make the most out of this last week and do a little bit more research into the relationship of cell autophagy and protein aggresomes.

I found a review article by Lamark & Johansen (2012), where they describe the process of aggrephagy, the selective degradation of protein aggregates by autophagy. Protein aggregates often present a serious threat to the viability of a cell, as they can sequester normal proteins and affect their functionality. This is why it’s critical for the cell to have built-in systems to deal with aggregation. One of these systems is the lysosomal degradation of intracellular contents through macroautophagy (it’s designed to degrade BIG things).

Macroautophagy begins by the formation of a phagophore, a double-sided membrane that scientists suspect originates from the endoplasmic reticulum, golgi apparatus, plasma membrane or mitochondria (they are not really sure where exactly). The phagophore then forms a closed vesicle, the autophagosome, which is transported to the microtubule-organizing center and fuses with lysosomes, an organelle full of strong degradative enzymes.

As a defense mechanisms against protein aggregates, the cell also promotes the formation of aggresomes. After all, it is easier to sequester and degrade one large structure of contained protein aggregates, than several aggregates spread out across the cell. One of the proteins that plays a key role in both the formation of aggresomes and their degradation through autophagy is histone deacetylase 6 (HDAC6). It is responsible for transporting protein aggregates to the aggresome, as well as regulating the actin cytoskeleton to transport the aggresomes to the autophagosome (Figure 1).

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Fig 1. Role of HDAC6 in aggresome formation and degradation. Source: Rodriguez-Gonzalez et al., 2008.

I have not even touched upon 90% of the information presented on the paper! As you can probably tell from this short summary, autophagy is an incredibly complex mechanism involving dozens of of pathways and cellular players. I hope to spend my first couple of weeks in the fall reading a little bit more about autophagy and its role aggresome degradation. There’s lots of literature to review!

Keep an eye out for my final post, where I will summarize my findings and progress this summer!

 

References:

Lamark, T., & Johansen, T. (2012). Aggrephagy: selective disposal of protein aggregates by macroautophagy. International journal of cell biology2012.

Rodriguez-Gonzalez, A., Lin, T., Ikeda, A. K., Simms-Waldrip, T., Fu, C., & Sakamoto, K. M. (2008). Role of the aggresome pathway in cancer: targeting histone deacetylase 6–dependent protein degradation. Cancer research68(8), 2557-2560.

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