Cellular cleanup! Atg40 folds the endoplasmic reticulum to facilitate its autophagy

July 22, 2020

The endoplasmic reticulum (ER) is an important part of eukaryotic cells (the type of cells that make up every living thing other than bacteria or viruses, including humans). They are a mass of tubes connected to the nucleus of the cell; the production of both proteins and lipids occur in the networks of the ER. For this organelle to properly function, cells routinely degrade portions of the ER so that it can be renewed. This process is called ER autophagy, or ER-phagy, where a structure called an "isolation membrane" expands and closes up to form an "autophagosome." The closure isolates various cellular materials including the ER within the autophagosome, which then transports the waste away for degradation.

While this process can be random, scientists have uncovered "autophagy receptors" that bind specifically to certain targets and interact with a group of proteins called Atg8, located on the isolation membrane. This interaction allows cells to target specific parts for degradation. In yeast, an organism commonly used for biological research, scientists have identified the protein Atg40 as an ER-phagy receptor, and also found that parts of its structure share similarities to a group of proteins called DP1/Yop1 (reticulon-like proteins), which "curves" the ER membranes into shape and maintains their tubular structures.

"Our previous work reveals that Atg40 is important for ER-phagy, but we actually know very little about how the process works," explained Dr. Hitoshi Nakatogawa of the Tokyo Tech, who led a team of scientists in research that investigated the mechanisms of Atg40 involvement in ER-phagy. "Because degradation of ER is so important for proper cellular function, gaining a better understanding of ER-phagy will improve basic biological knowledge."

Their experiments with yeast, the findings of which are published in Nature Communications, showed that Atg40 is important for "curving and folding" the ER membrane, and therefore has a similar function to DP1/Yop1, explaining their structural similarities. Atg40 is also necessary for ER-phagy, specifically being involved in breaking up the ER membrane so that it can be imbibed by autophagosomes. Researchers demonstrated that during this folding and fragmentation of the ER, Atg40 forms a protein assembly (cluster of proteins) by interacting with Atg8 located specifically at points of contact between the ER and the isolation membrane (as shown in Figure 1). In other words, Atg40 does not randomly or always remodel ER structure; it does so only for the ER parts that will be degraded.

Regarding the significance of these results, Dr. Nakatogawa commented: "What I find particular exciting is the insight we gained on a crucial part of how cells work, how they deal with waste or get rid of abnormal cell parts. Our work doesn't just have implications for ER-phagy though, it can also potentially tell us something about how other organelles, like the nucleus or mitochondria, are degraded."

Besides just being valuable basic research, these findings also have significant practical applications. Knowing the mechanisms of organelle degradation might help the development of drugs that target this process if it breaks down. This presents potential attractive solutions for diseases involving the malfunction of ER such as sensory neuropathy.
-end-


Tokyo Institute of Technology

Related Proteins Articles from Brightsurf:

New understanding of how proteins operate
A ground-breaking discovery by Centenary Institute scientists has provided new understanding as to the nature of proteins and how they exist and operate in the human body.

Finding a handle to bag the right proteins
A method that lights up tags attached to selected proteins can help to purify the proteins from a mixed protein pool.

Designing vaccines from artificial proteins
EPFL scientists have developed a new computational approach to create artificial proteins, which showed promising results in vivo as functional vaccines.

New method to monitor Alzheimer's proteins
IBS-CINAP research team has reported a new method to identify the aggregation state of amyloid beta (Aβ) proteins in solution.

Composing new proteins with artificial intelligence
Scientists have long studied how to improve proteins or design new ones.

Hero proteins are here to save other proteins
Researchers at the University of Tokyo have discovered a new group of proteins, remarkable for their unusual shape and abilities to protect against protein clumps associated with neurodegenerative diseases in lab experiments.

Designer proteins
David Baker, Professor of Biochemistry at the University of Washington to speak at the AAAS 2020 session, 'Synthetic Biology: Digital Design of Living Systems.' Prof.

Gone fishin' -- for proteins
Casting lines into human cells to snag proteins, a team of Montreal researchers has solved a 20-year-old mystery of cell biology.

Coupled proteins
Researchers from Heidelberg University and Sendai University in Japan used new biotechnological methods to study how human cells react to and further process external signals.

Understanding the power of honey through its proteins
Honey is a culinary staple that can be found in kitchens around the world.

Read More: Proteins News and Proteins Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.