Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cell energy sensor mechanism discovered

22.02.2012
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: http://www.hopkinsmedicine.org/news/media/releases/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: http://www.hopkinsmedicine.org/institute_basic_biomedical_sciences/about_us

/scientists/jef_boeke.html

Johns Hopkins Researchers Find Link Between Cell's Energy Use and Genome Health: http://www.hopkinsmedicine.org/Press_releases/2006/07_21a_06.html

On the Web: Jef Boeke's lab: http://www.bs.jhmi.edu/MBG/boekelab/

The High Throughput Biology Center: http://www.hopkinsmedicine.org/institute_basic_biomedical_sciences/research

_centers/high_throughput_biology_hit/

Department of Molecular Biology and Genetics: http://www.mbg.jhmi.edu/Pages/index.aspx

Vanessa McMains | EurekAlert!
Further information:
http://www.jhmi.edu

More articles from Life Sciences:

nachricht Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel

nachricht Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown 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: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Scientist invents way to trigger artificial photosynthesis to clean air

26.04.2017 | Materials Sciences

Ammonium nitrogen input increases the synthesis of anticarcinogenic compounds in broccoli

26.04.2017 | Agricultural and Forestry Science

SwRI-led team discovers lull in Mars' giant impact history

26.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>