Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Salk scientists uncover how a cell's 'fuel gauge' promotes healthy development

26.04.2016

Salk scientists have revealed how a cellular "fuel gauge" responsible for monitoring and managing cells' energy processes also has an unexpected role in development. This critical link could help researchers better understand cancer and diabetes pathways.

This cellular fuel gauge is a protein complex called AMPK that oversees energy input and output to keep the cell running smoothly. If AMPK were a car sensor, for instance, it would be able to instruct the vehicle when to get gas or lower the air conditioning to save energy.


Salk scientists reveal a close association between lysosomes, the recycling centers of the cell, and the development of the endodermal germ layer. This image shows a well-differentiated structure derived from normal embryonic stem cells, with all nuclei stained blue. Only endoderm cells (green) contain high levels of lysosomes (red).

Credit: Anwesh Kamireddy/Salk Institute

Similarly, if the cell's fuel supply--nutrients--is scarce, AMPK slows down cell growth and changes its metabolism. Previously, Salk Professor Reuben Shaw discovered that AMPK could halt tumors' revved-up metabolism, as well as restore normal function to the liver and other tissues in diabetics.

"Even though there's great interest in AMPK related to diabetes and cancer, frankly nothing was known about how this fuel gauge process changes in different cell populations during development," says Shaw, senior author of the work and holder of the William R. Brody Chair. Aside from giving new insight into stem cell therapies, the work, published in March 2016 in Genes & Development, could also help refine cancer treatments.

"To begin, we used CRISPR technology to edit out two important components of the AMPK pathway in embryonic stem cells," says Nathan Young, Salk research associate and first author of the paper. "At first we didn't see any difference, but things became interesting when we prompted the cells to differentiate."

Normally, embryonic stem cells have the capacity to generate more specialized cells that belong to one of three broad groups termed germ layers--the endoderm, ectoderm and mesoderm--that can ultimately develop into all of the diverse cell types in an organism. However, the cells without a functioning AMPK pathway failed to efficiently make endoderm (the innermost layer in an organism) and instead made too much ectoderm (the layer that would turn into skin).

"These cells couldn't make the right choice," says Shaw. "This was the first inclination that this metabolic pathway is telling cells what kind of specialized tissues to become."

What was remarkable, according to the researchers, is when they looked closer at the gene expression patterns of the AMPK-deficient cells. They found that a large number of down-regulated genes related to one specific cellular structure: the lysosome. This critical self-contained organelle contains corrosive enzymes that degrade cellular material to reuse components--the garbage disposal and recycling center of the cell.

This loss of lysosomes, the researchers discovered, was due to the loss of a transcription factor called Tfeb, which turns on the expression of lysosomal genes in times of starvation. By simply reintroducing Tfeb into the dysfunctional cells, the team was able to restore normal development and differentiation.

"It was thought that lysosomes and AMPK were connected somehow, but no one had dreamed that you'd get no lysosomes if you don't have this fuel gauge," says Shaw. "Connecting the AMPK pathway to lysosomes begs the question of whether this pathway is part of anti-cancer pathways as well."

Currently, lysosome inhibitors are in dozens of clinical trials for breast, lung, pancreatic and brain cancers, even though the exact link between lysosomes and tumors are not understood. "We are decoding some of these underlying connections that might indicate when and how a cancer drugs might be useful," says Shaw. "This work may also help up make better, more specific ways of targeting lysosomes in cancer."

###

Other authors were Anwesh Kamireddy, Jeanine Van Nostrand, Lillian Eichner, Maxim Nikolaievich Shokhirev and Yelena Dayn, all of the Salk Institute. The work was supported by the National Institutes of Health and the Leona M. and Harry B. Helmsley Charitable Trust.

About the Salk Institute for Biological Studies:

Every cure has a starting point. The Salk Institute embodies Jonas Salk's mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer's, aging or diabetes, Salk is where cures begin.

Media Contact

Salk Communications
press@salk.edu
858-453-4100

 @salkinstitute

http://www.salk.edu 

Salk Communications | EurekAlert!

Further reports about: embryonic stem embryonic stem cells genes lysosome lysosomes stem cells tumors

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>