Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Sweet genes

04.07.2014

New way found by which metabolism is linked to the regulation of DNA

A research team at the Faculty of Medicine & Dentistry at the University of Alberta have discovered a new way by which metabolism is linked to the regulation of DNA, the basis of our genetic code. The findings may have important implications for the understanding of many common diseases, including cancer.

The DNA wraps around specialized proteins called histones in the cell's nucleus. Normally, histones keep the DNA tightly packaged, preventing the expression of genes and the replication of DNA, which are required for cell growth and division.

In order for these critical functions to take place, histones need to be modified with the attachment of an acetyl-group, donated by a critical molecule called acetyl-CoA. This attachment relaxes the DNA, allowing for DNA replication and gene expression. This mechanism is called "epigenetic regulation of DNA" and is important for normal functions (like the growth of an embryo or brain functions) or in common diseases like heart failure or cancer. Until now, how the nucleus generates acetyl-CoA for histone acetylation had remained elusive.

The research team, lead by postdoctoral fellow Gopinath Sutendra and professor Evangelos Michelakis in the Department of Medicine, discovered that an enzyme thought to reside only within mitochondria, called Pyruvate Dehydrogenase Complex (PDC), can actually find its way into the nucleus and do what it is designed to do in the mitochondria: generate acetyl-CoA. When in mitochondria, PDC uses the carbohydrates from our diet to generate acetyl-CoA for energy production. When in the nucleus, PDC can produce acetyl-CoA for histone acetylation.

"Although this jumping of an enzyme from one organelle into another in the cell is not unheard off, our results were quite surprising", Sutendra says. "We wanted to measure acetyl-CoA levels and PDC in the mitochondria because that's where we thought they were. But accidentally we had the nuclei isolated at the same time and we saw PDC in the nucleus. So we asked, 'what is PDC doing there?' And that started it all."

"We were surprised that, despite the recognized importance of histone acetylation in cell biology and medicine, and despite the efforts by many to develop drugs that regulate histone acetylation, the source of acetyl-CoA in the nucleus had remained unknown," Michelakis says. "Sometimes the answers to important biological questions are just next to you, waiting to be discovered," he adds.

The team found that the translocation of PDC into the nucleus made cancer cells grow faster, an observation that may lead to additional strategies in the war against cancer. Yet, because the findings relate to how our DNA is regulated in general, this work may have far broader implications for many physiologic or pathologic conditions where epigenetic regulation is critical. "We are very excited about this new pathway linking energy production (the process known as metabolism) with gene regulation," the researchers say.

The work is published in the July 3, 2014, issue of the journal Cell. Michelakis is particularly proud of the fact that this is the product of a team that is entirely based at the University of Alberta. Many young researchers in the Department of Medicine like Adam Kinnaird, Peter Dromparis and Roxane Paulin were critical members of the team that also included technicians (Trevor Stenson, Alois Haromy, Kyoko Hashimoto) and researchers from the NanoFAB facility (Nancy Zhang, Eric Flaim). The work was funded by the Canadian Institutes for Health Research and the Hecht Foundation (Vancouver, Canada).

For more information, or to arrange an interview, please contact:

Ross Neitz, Communications Associate
Faculty of Medicine & Dentistry, University of Alberta
Tel: (w) 780-492-5986, (c) 780-297-8354
rneitz@ualberta.ca

Ross Neitz | Eurek Alert!
Further information:
http://www.med.ualberta.ca/

Further reports about: DNA Dentistry Medicine acetylation diseases enzyme epigenetic genes histones metabolism mitochondria replication

More articles from Life Sciences:

nachricht A new potential biomarker for cancer imaging
05.02.2016 | Universiti Putra Malaysia (UPM)

nachricht NIH researchers identify striking genomic signature shared by 5 types of cancer
05.02.2016 | NIH/National Human Genome Research Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Automated driving: Steering without limits

OmniSteer project to increase automobiles’ urban maneuverability begins with a € 3.4 million budget

Automobiles increase the mobility of their users. However, their maneuverability is pushed to the limit by cramped inner city conditions. Those who need to...

Im Focus: Microscopy: Nine at one blow

Advance in biomedical imaging: The University of Würzburg's Biocenter has enhanced fluorescence microscopy to label and visualise up to nine different cell structures simultaneously.

Fluorescence microscopy allows researchers to visualise biomolecules in cells. They label the molecules using fluorescent probes, excite them with light and...

Im Focus: NASA's ICESat-2 equipped with unique 3-D manufactured part

NASA's follow-on to the successful ICESat mission will employ a never-before-flown technique for determining the topography of ice sheets and the thickness of sea ice, but that won't be the only first for this mission.

Slated for launch in 2018, NASA's Ice, Cloud and land Elevation Satellite-2 (ICESat-2) also will carry a 3-D printed part made of polyetherketoneketone (PEKK),...

Im Focus: Sinking islands: Does the rise of sea level endanger the Takuu Atoll in the Pacific?

In the last decades, sea level has been rising continuously – about 3.3 mm per year. For reef islands such as the Maldives or the Marshall Islands a sinister picture is being painted evoking the demise of the island states and their cultures. Are the effects of sea-level rise already noticeable on reef islands? Scientists from the ZMT have now answered this question for the Takuu Atoll, a group of Pacific islands, located northeast of Papua New Guinea.

In the last decades, sea level has been rising continuously – about 3.3 mm per year. For reef islands such as the Maldives or the Marshall Islands a sinister...

Im Focus: Energy-saving minicomputers for the ‘Internet of Things’

The ‘Internet of Things’ is growing rapidly. Mobile phones, washing machines and the milk bottle in the fridge: the idea is that minicomputers connected to these will be able to process information, receive and send data. This requires electrical power. Transistors that are capable of switching information with a single electron use far less power than field effect transistors that are commonly used in computers. However, these innovative electronic switches do not yet work at room temperature. Scientists working on the new EU research project ‘Ions4Set’ intend to change this. The program will be launched on February 1. It is coordinated by the Helmholtz-Zentrum Dresden-Rossendorf (HZDR).

“Billions of tiny computers will in future communicate with each other via the Internet or locally. Yet power consumption currently remains a great obstacle”,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

AKL’16: Experience Laser Technology Live in Europe´s Largest Laser Application Center!

02.02.2016 | Event News

From intelligent knee braces to anti-theft backpacks

26.01.2016 | Event News

DATE 2016 Highlighting Automotive and Secure Systems

26.01.2016 | Event News

 
Latest News

A new potential biomarker for cancer imaging

05.02.2016 | Life Sciences

Graphene is strong, but is it tough?

05.02.2016 | Materials Sciences

Tiniest Particles Shrink Before Exploding When Hit With SLAC's X-ray Laser

05.02.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>