Nav: Home

Autophagy degrades liquid droplets, but not aggregates, of proteins

February 13, 2020

Under JST's Strategic Basic Research Programs, Noda Nobuo (Laboratory Head) and Yamasaki Akinori, Postdoctoral Fellow (currently Assistant Professor, Tokyo Institute of Technology), at the Institute of Microbial Chemistry in collaboration with other researchers, have discovered that autophagy is effective for selectively degrading protein in a state of liquid droplet(1) that is formed through liquid-liquid phase separation(2) but does poorly with the degradation of protein in aggregation or solid state.

Autophagy is one of the mechanisms through which cellular protein is degraded. There exists a selective type of autophagy named selective autophagy(3) that targets and degrades specific proteins and organelles. It has been assumed that selective autophagy prevents the onset of diseases, but the state of proteins in which they could be efficiently degraded had been unclear.

This research group used the selective autophagy of Ape1 protein in yeast as the model system and succeeded in reconstituting the Ape1 isolation process with a lipid membrane in a test tube. It revealed that Ape1 protein is effectively isolated by the lipid membrane through the functioning of the Atg8 and receptor proteins when Ape1 forms droplets but is not isolated by the lipid membrane when Ape1 forms aggregates.

The discovery that selective autophagy is effective in degrading protein droplets but does poorly in degrading protein aggregates indicates that the activation of autophagy alone is insufficient in the prevention of and therapeutic medication development for neurodegenerative diseases and other diseases that are believed to be caused by the accumulation of abnormal proteins and that it is important to develop drugs that change aggregations into droplets. This will hopefully lead to the discovery of drugs that target "liquid-liquid phase separation," which is the mechanism for creating droplets.

It was also proved for the first time that the isolation step for the targeted protein in selective autophagy can be conducted with just the Atg8 and receptor proteins. Autophagy also selectively degrades mitochondria and other organelles as well as pathogenic bacteria. Atg8 and receptor proteins could be responsible for selective isolation in a similar mechanism in these cases as well. The application of the test-tube reconstitution system developed here would promote research on the selective autophagy mechanisms for a wide variety of targets.

(1) Liquid droplet

A condensate of macromolecules with fluidity created when protein and/or nucleic acids undergo liquid-liquid phase separation. The droplets are also known as "membraneless organelles" and perform various functions within the cell. A droplet spontaneously assumes a spherical form. It also has high internal fluidity, and it actively exchanges molecules with its surroundings.

(2) Liquid-liquid phase separation

This is the phenomenon of a uniform liquid phase separating into multiple liquid phases. It is observed in daily life as the separation of water and oil, which occurs within cells with proteins and nucleic acids.

(3) Selective autophagy?

Autophagic pathway that degrades specific targets when it is required by the cell, unlike ordinary autophagy, which is triggered by starvation and degrades intracellular components indiscriminately. In selective autophagy, there are receptor proteins that recognize the wide variety of targets for degradation. It is believed that they all selectively load their targets into autophagosomes by connecting to both the degradation targets and the Atg8 proteins on the autophagosomes.
-end-


Japan Science and Technology Agency

Related Autophagy Articles:

Autophagy degrades liquid droplets, but not aggregates, of proteins
Autophagy is a mechanism through which cellular protein is degraded.
Autophagy genes act as tumor suppressors in ovarian cancer
Researchers at the Medical University of South Carolina and University of California at San Diego report in PLOS Genetics that the loss of BECN1 promoted early ovarian cancer formation and genomic instability.
Mechanism of controlling autophagy by liquid-liquid phase separation revealed
Japanese scientists elucidated characteristics of PAS through observing the Atg protein using a fluorescence microscope and successfully reconstituted PAS in vitro.
New membranes for cellular recycling
Cells produce the shell of the autophagosomes on the spot.
West Nile virus triggers brain inflammation by inhibiting protein degradation
West Nile virus (WNV) inhibits autophagy -- an essential system that digests or removes cellular constituents such as proteins -- to induce the aggregation of proteins in infected cells, triggering cell death and brain inflammation (encephalitis), according to Hokkaido University researchers.
The molecule that can AUTAC bad proteins
Tohoku University researchers have developed a strategy that could help cells get rid of disease-related debris.
Clearing damaged cells out of the body helps heal diabetics' blood vessels
Research published today in Experimental Physiology shows that ramping up one of the body's waste disposal system, called autophagy, helps heal the blood vessels of diabetics.
How the cellular recycling system is put on hold while cells divide
Research involving several teams at the Babraham Institute, Cambridge, UK, has shown that cellular recycling (autophagy) is repressed during the process of cell division, and how repression of autophagy during mitosis utilises a different master regulator.
Insight into cells' 'self-eating' process could pave the way for new dementia treatments
Cells regularly go through a process called autophagy -- literally translated as 'self-eating' -- which helps to destroy bacteria and viruses after infection.
Deregulated mTOR is responsible for autophagy defects exacerbating kidney stone formation
Kidney stone disease is a lifestyle-related disease prevalent; however, effective medical treatment for the disease is not yet well established.
More Autophagy News and Autophagy Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Uncharted
There's so much we've yet to explore–from outer space to the deep ocean to our own brains. This hour, Manoush goes on a journey through those uncharted places, led by TED Science Curator David Biello.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Dispatch 1: Numbers
In a recent Radiolab group huddle, with coronavirus unraveling around us, the team found themselves grappling with all the numbers connected to COVID-19. Our new found 6 foot bubbles of personal space. Three percent mortality rate (or 1, or 2, or 4). 7,000 cases (now, much much more). So in the wake of that meeting, we reflect on the onslaught of numbers - what they reveal, and what they hide.  Support Radiolab today at Radiolab.org/donate.