Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Cell energy sensor mechanism discovered

Studies linked to better understanding of cancer drugs

Johns Hopkins and National Taiwan University researchers have discovered more details about how an energy sensing "thermostat" protein determines whether cells will store or use their energy reserves.

In a report in the Feb. 9 edition of Nature, the researchers showed that a chemical modification on the thermostat protein changes how it's controlled. Without the modification, cells use stored energy, and with it, they default to stockpiling resources. When cells don't properly allocate their energy supply, they can die off or become cancerous. The Johns Hopkins team focused especially on enzymes that add or remove so-called acetyl groups from protein molecules.

"Understanding how cells are affected by adding acetyl groups to proteins, particularly those involved in energy use, is important because there is increasing use of drugs that block acetyl-removing enzymes for treatment of cancer and neurodegenerative diseases," says Jef Boeke, Ph.D., professor of molecular biology, genetics and oncology, and director of the High Throughput Biology Center at the Johns Hopkins University School of Medicine. "Blocking acetyl-removing enzymes turns on anticancer genes that help fight cancer; however, it is not known what other genes and cellular processes may also be affected by these treatments."

To determine which enzymes remove acetyl chemical groups from which proteins, the researchers engineered human cells with reduced levels of each of 12 enzymes known to remove acetyl chemical groups. In each of these cell lines, they then turned down each of about 20,000 genes and used a DNA "chip" to identify which genes were affected by reduced levels of the acetyl-removing enzymes. The DNA chip highlighted a specific interaction between the thermostat protein, AMP-activated protein kinase (AMPK), and one of the acetyl-removing enzymes, HDAC1.

With less HDAC, AMPK was turned "off," presumably because it retains its acetyl group, the researchers concluded. AMPK acts like an energy thermostat because when energy levels are low in the cell, AMPK kick-starts processes that use the cell's energy reserves and cuts off reactions that store energy. On the other hand, when the cell has plenty of energy, AMPK turns off, causing energy in the form of sugar and fats being stored for later use.

Because the HDAC1 protein turned on AMPK, the researchers presumed there would be a corresponding acetyl-adding enzyme to specifically turn off AMPK. To find this enzyme, they extracted AMPK protein from eight different cell lines, each with reduced levels of a type of acetyl-adding enzyme. They found that AMPK in cells with reduced levels of this acetyl-adding enzyme, called p300, was less acetylated than in cells containing normal amounts of p300.

To confirm the idea that adding or removing acetyl groups directly affects how AMPK controls the way the cell uses energy, they measured the cell's energy stores with the help of a dye that accumulates in the fat globules of a cell. The dye let them estimate the size of fat globules that store energy. The cells unable to add acetyl to AMPK contained less of the dye and therefore smaller fat globules compared to normal human cells. Conversely, the cells unable to remove acetyl groups from AMPK contained more of the dye, indicating bigger fat globules. The research team concluded that when AMPK contains acetyl groups the cell uses less of its energy reserves than when AMPK does not contain acetyl groups.

Boeke says the work on human cells followed similar studies on yeast energy proteins done earlier in his laboratory.

Additional authors of the study include Yu-yi Lin, Shang-Yun Liu and Yi-hsuan Chou of the National Taiwan University; Jin-ying Lu of the National Taiwan University Hospital; Chin Ni Khnor and Chi-Long Lin of Academia Sinica, Taipei, Taiwan; Samara Kiihl and Rafael Irizarry of the Johns Hopkins University Bloomberg School of Public Health; and Yasir Suhail, Zheng Kuang and Joel Bader of the Johns Hopkins University School of Medicine.

The study was supported by funds from National Science Council grants, National Taiwan University Frontier and Innovative Research, National Taiwan University Excellent Translational Medicine Research Project, a National Health Research Institutes Career Development grant, the Liver Disease Prevention and Treatment Research Foundation and a National Institutes of Health Common Fund grant.

Related Stories: Hopkins Scientists Turn on Fountain of Youth in Yeast:


Jef Boeke of Molecular Biology and Genetics and the HiT Center on microarrays 101 and scientific nomenclature:


Johns Hopkins Researchers Find Link Between Cell's Energy Use and Genome Health:

On the Web: Jef Boeke's lab:

The High Throughput Biology Center:


Department of Molecular Biology and Genetics:

Vanessa McMains | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Biologists unravel another mystery of what makes DNA go 'loopy'
16.03.2018 | Emory Health Sciences

nachricht Scientists map the portal to the cell's nucleus
16.03.2018 | Rockefeller University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.

When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...

Im Focus: Radar for navigation support from autonomous flying drones

At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.

Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

International Virtual Reality Conference “IEEE VR 2018” comes to Reutlingen, Germany

08.03.2018 | Event News

Latest News

Wandering greenhouse gas

16.03.2018 | Earth Sciences

'Frequency combs' ID chemicals within the mid-infrared spectral region

16.03.2018 | Physics and Astronomy

Biologists unravel another mystery of what makes DNA go 'loopy'

16.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>