Mechanism behind autophagy trigger unveiled
en-GBde-DEes-ESfr-FR

Mechanism behind autophagy trigger unveiled

24.09.2024 Osaka University

A research team led by Osaka University has uncovered a novel mechanism essential for initiating autophagy.

Osaka, Japan – An international research team led by Osaka University has identified a new mechanism crucial for the initiation of autophagy, a self-degradation process cells use to eliminate unneeded or damaged components. In recent years, autophagy has also been recognized for its roles in aging and lifespan regulation.

During autophagy, intracellular molecules and structures are sequestered within a membrane-bound structure known as an autophagosome, which is subsequently degraded in lysosomes. It is well-established that the formation of autophagosomes involves the coordinated action of multiple autophagy-related proteins.

Previously, the research group revealed that autophagosome formation takes place on the endoplasmic reticulum membrane in close proximity to mitochondria within cells. They also discovered that the PI3K complex, an autophagy-related protein, is essential for this formation process. The activity of the PI3K complex is controlled by the ULK1 complex.

The ULK1 complex is known to translocate from the cytoplasm to the endoplasmic reticulum membrane, where autophagosomes are formed at the onset of autophagy. However, the underlying mechanism and significance of this process were not fully understood until now. In a recent article published in Nature Communications, the research team revealed that the palmitoylation of ULK1 triggers a series of reactions that initiate autophagy.

The team identified ZDHHC13, a palmitoylation enzyme, as a key player in this process through their search for intracellular factors involved in the initiation of autophagy.

Mutations of ZDHHC13 have been linked to various diseases, including Huntington’s disease, while autophagy is also implicated in the development and progression of conditions such as cancer and neurodegenerative disorders.

Senior author Maho Hamasaki explained, “Our team discovered that ZDHHC13 palmitoylates ULK1, thereby localizing the ULK1 complex to autophagosome formation sites. This palmitoylation is also involved in the phosphorylation of the ATG14L protein within the PI3K complex, which in turn regulates the activity of the PI3K complex.”

Understanding the molecular mechanisms that initiate autophagy is expected to enhance our knowledge of autophagy-related diseases.

Lead author Keisuke Tabata added, “Autophagy not only provides a nutrient source through intracellular degradation but also plays a crucial role in maintaining normal cellular function and preventing various pathologies. We will continue to investigate how autophagy begins, furthering our understanding of the mechanisms behind related diseases.”

###

The article, “Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy,” was published in Nature Communications at DOI: https://doi.org/10.1038/s41467-024-51402-w

Title: Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy
Journal: Nature Communications
DOI: 10.1038/s41467-024-51402-w
Funded by: Japan Society for the Promotion of Science, JST CREST, JSPS KAKENHI, Grant-in-Aid for Scientific Research on Innovative Areas, Ono Medical Research Foundation, UCL-OU seed fund and MSD Life Science Foundation
Angehängte Dokumente
  • Figure: Upon autophagy induction, ZDHHC13 is recruited to autophagosome formation sites together with ATG9A. ULK1 is palmitoylated at Cys927 and Cys1003 residues by ZDHHC13, and the ULK1 complex are anchored to an autophagosome formation site. The palmitoylation of ULK1 promotes phosphorylation of ATG14L which leads VPS34 activation. Activated PI3-kinase complex produces PI3P at autophagosome formation sites. These sequential reactions trigger efficient autophagy induction., Original content, Credit must be given to the creator., Keisuke Tabata
24.09.2024 Osaka University
Regions: Asia, Japan
Keywords: Health, Medical

Disclaimer: AlphaGalileo is not responsible for the accuracy of news releases posted to AlphaGalileo by contributing institutions or for the use of any information through the AlphaGalileo system.

Referenzen

We have used AlphaGalileo since its foundation but frankly we need it more than ever now to ensure our research news is heard across Europe, Asia and North America. As one of the UK’s leading research universities we want to continue to work with other outstanding researchers in Europe. AlphaGalileo helps us to continue to bring our research story to them and the rest of the world.
Peter Dunn, Director of Press and Media Relations at the University of Warwick
AlphaGalileo has helped us more than double our reach at SciDev.Net. The service has enabled our journalists around the world to reach the mainstream media with articles about the impact of science on people in low- and middle-income countries, leading to big increases in the number of SciDev.Net articles that have been republished.
Ben Deighton, SciDevNet
AlphaGalileo is a great source of global research news. I use it regularly.
Robert Lee Hotz, LA Times

Wir arbeiten eng zusammen mit...


  • BBC
  • The Times
  • National Geographic
  • The University of Edinburgh
  • University of Cambridge
  • iesResearch
Copyright 2024 by DNN Corp Terms Of Use Privacy Statement