Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Sweet genes


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

Ross Neitz | Eurek Alert!
Further information:

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

More articles from Life Sciences:

nachricht Molecular trigger for Cerebral Cavernous Malformation identified
26.11.2015 | EMBO - excellence in life sciences

nachricht Peering into cell structures where neurodiseases emerge
26.11.2015 | University of Delaware

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Climate study finds evidence of global shift in the 1980s

Planet Earth experienced a global climate shift in the late 1980s on an unprecedented scale, fuelled by anthropogenic warming and a volcanic eruption, according to new research published this week.

Scientists say that a major step change, or ‘regime shift’, in the Earth’s biophysical systems, from the upper atmosphere to the depths of the ocean and from...

Im Focus: Innovative Photovoltaics – from the Lab to the Façade

Fraunhofer ISE Demonstrates New Cell and Module Technologies on its Outer Building Façade

The Fraunhofer Institute for Solar Energy Systems ISE has installed 70 photovoltaic modules on the outer façade of one of its lab buildings. The modules were...

Im Focus: Lactate for Brain Energy

Nerve cells cover their high energy demand with glucose and lactate. Scientists of the University of Zurich now provide new support for this. They show for the first time in the intact mouse brain evidence for an exchange of lactate between different brain cells. With this study they were able to confirm a 20-year old hypothesis.

In comparison to other organs, the human brain has the highest energy requirements. The supply of energy for nerve cells and the particular role of lactic acid...

Im Focus: Laser process simulation available as app for first time

In laser material processing, the simulation of processes has made great strides over the past few years. Today, the software can predict relatively well what will happen on the workpiece. Unfortunately, it is also highly complex and requires a lot of computing time. Thanks to clever simplification, experts from Fraunhofer ILT are now able to offer the first-ever simulation software that calculates processes in real time and also runs on tablet computers and smartphones. The fast software enables users to do without expensive experiments and to find optimum process parameters even more effectively.

Before now, the reliable simulation of laser processes was a job for experts. Armed with sophisticated software packages and after many hours on computer...

Im Focus: Quantum Simulation: A Better Understanding of Magnetism

Heidelberg physicists use ultracold atoms to imitate the behaviour of electrons in a solid

Researchers at Heidelberg University have devised a new way to study the phenomenon of magnetism. Using ultracold atoms at near absolute zero, they prepared a...

All Focus news of the innovation-report >>>



Event News

Fraunhofer’s Urban Futures Conference: 2 days in the city of the future

25.11.2015 | Event News

Gluten oder nicht Gluten? Überempfindlichkeit auf Weizen kann unterschiedliche Ursachen haben

17.11.2015 | Event News

Art Collection Deutsche Börse zeigt Ausstellung „Traces of Disorder“

21.10.2015 | Event News

Latest News

Using sphere packing models to explain the structure of forests

26.11.2015 | Ecology, The Environment and Conservation

Dimensionality transition in a newly created material

26.11.2015 | Materials Sciences

Revealing glacier flow with animated satellite images

26.11.2015 | Earth Sciences

More VideoLinks >>>