Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Surviving in starvation - New mechanism for cell preservation discovered

16.05.2018

Scientists from the Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) in cooperation with the Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA, discovered a new mechanism that is important for cells to survive starvation. The protein NUFIP1, which normally occurs in the cell nucleus, migrates into the cytoplasm when there is a lack of nutrients and binds to ribosomes, which are then marked for degradation; an important survival strategy of the cell to ensure the maintenance of the cell upon starvation. The research results were now published in the renowned journal Science.

The recycling program of cells is autophagy; a fundamental component of the cellular quality control and extremely important for maintaining cell functionality. Degradation of misfolded proteins or damaged organelles through autophagy prevents negative effects on the cell and allows nutrients recycling so they can be used by the cell to build up new components. Errors in this recycling process can lead to cancer, neurodegenerative diseases and increased susceptibility to infections, and they can also affect ageing.


The protein NUFIP1 is necessary for the ribosomal degradation under starvation and ensures the survival of cells in hunger situations.

(Figure: FLI / Magdalena Voll; Source: u.a. Wikipedia)

Under normal conditions, autophagy takes place only to a small extent; however it is activated under nutrient starvation, e.g. deficiency of amino acids. It is known, that the “mechanistic target of rapamycin complex 1” (mTORC1), the major nutrient-sensitive regulator of growth, plays an important role in this process. It regulates the flow of macromolecules intended for degradation to the "stomach of the cell", the lysosomes. How this intracellular regulation works under starvation and what proteins play a role in it, are still open questions.

Insights into the recycling process of the cell

Researchers from the lab of Alessandro Ori at the Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) followed these questions in cooperation with the lab of David M. Sabatini from the Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA. They performed quantitative proteomic analyses to analyze the lysosomal proteome under conditions that inhibit the mTORC1 pathway. They examined lysosomes in nutrient-replete media (full media), under conditions of starvation, through deficiency of amino acids and glucose, and under conditions that inhibit mTOR kinase through torin1.

“Thanks to the LysoIP method that was developed in the Sabatini Lab and the advanced mass spectrometry platform of the FLI core facility proteomics, we were able to profile the dynamics of the lysosomal proteome under different conditions of mTORC1 activation”, tells Dr. Alessandro Ori, Junior Group Leader at the FLI. The international team identified more than 800 proteins associated with lysosomes. “Of these many proteins, the Nuclear fragile X mental retardation-interacting protein 1 (NUFIP1) piqued our interest, because its lysosomal abundance increased upon the inhibition of mTORC1 pathway.”

Migration of NUFIP1 upon mTOR inhibition

Previous work indicates that NUFIP1 is largely a nuclear protein but it has also been observed in the cytoplasm of some cell types. With biochemical assays and imaging studies the collaborators from MIT were able to confirm that the inhibition of mTOR caused NUFIP1 to translocate from the nucleus to autophagosomes and lysosomes. “These are both cell components that play an important role in autophagy”, underlines Dr. Ori.

NUFIP1 is important to survive starvation

With these “snapshots into the cells” the researchers were able to identify this new role of the protein NUFIP1, as it was previously unknown that it is also associated with lysosomes. Upon starvation NUFIP1 binds intact ribosomes and targets them for degradation in the lysosomes. Ribosomes, the “protein factory” of cells, are large complexes made up of proteins and RNAs. They are among the most abundant components of cells and, as such, they represent one of the most important reserves of nutrients. “We were now able to show that NUFIP1 is necessary for ribosomal degradation upon starvation in human and mouse cells and with that ensures the survival of the cell in hunger situations", emphasizes Dr. Ori.

The results of the research team from Germany and the USA underline that the protein NUFIP1 plays an important role in the selective autophagy of ribosomes in cases of nutrient starvation in mammalian cells. This work exemplifies how the study of the dynamics of organelle proteomes can reveal fundamental mechanisms that are relevant for biomedical and aging research.

Publication

NUFIP1 is a ribosome receptor for starvation-induced ribophagy. Gregory A. Wyant, Monther Abu-Remaileh, Evgeni M. Frenkel, Nouf N. Laqtom, Vimisha Dharamdasani, Caroline A. Lewis, Sze Ham Chan, Ivonne Heinze, Alessandro Ori, David M. Sabatini. Science 2018, eaar2663, DOI: 10.1126/science.aar2663. http://science.sciencemag.org/content/early/2018/04/25/science.aar2663?rss=1

Contact

Dr. Kerstin Wagner
Press and Public Relations
Phone: 03641-656378
Email: presse@leibniz-fli.de


Background information

The Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) – upon its inauguration in 2004 – was the first German research organization dedicated to research on the process of aging. More than 330 employees from over 30 nations explore the molecular mechanisms underlying aging processes and age-associated diseases. For more information, please visit http://www.leibniz-fli.de.

The Leibniz Association connects 93 independent research institutions that range in focus from the natural, engineering and environmental sciences via economics, spatial and social sciences to the humanities. Leibniz Institutes address issues of social, economic and ecological relevance. They conduct knowledge-driven and applied basic research, maintain scientific infrastructure and provide research-based services. The Leibniz Association identifies focus areas for knowledge transfer to policy-makers, academia, business and the public. Leibniz Institutes collaborate intensively with universities – in the form of “WissenschaftsCampi” (thematic partnerships between university and non-university research institutes), for example – as well as with industry and other partners at home and abroad. They are subject to an independent evaluation procedure that is unparalleled in its transparency. Due to the institutes’ importance for the country as a whole, they are funded jointly by the Federation and the Länder, employing some 19,100 individuals, including 9,900 researchers. The entire budget of all the institutes is approximately 1.9 billion EUR. See http://www.leibniz-association.eu for more information.

Weitere Informationen:

http://www.leibniz-fli.de - Website Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) Jena

Dr. Kerstin Wagner | idw - Informationsdienst Wissenschaft

Further reports about: Alternsforschung FLI Fritz-Lipmann-Institut Sabatini lysosomes mTOR mTORC1 proteins

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>