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 Great apes communicate cooperatively
25.05.2016 | Max-Planck-Institut für Ornithologie

nachricht Rice study decodes genetic circuitry for bacterial spore formation
24.05.2016 | Rice 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: Computational high-throughput screening finds hard magnets containing less rare earth elements

Permanent magnets are very important for technologies of the future like electromobility and renewable energy, and rare earth elements (REE) are necessary for their manufacture. The Fraunhofer Institute for Mechanics of Materials IWM in Freiburg, Germany, has now succeeded in identifying promising approaches and materials for new permanent magnets through use of an in-house simulation process based on high-throughput screening (HTS). The team was able to improve magnetic properties this way and at the same time replaced REE with elements that are less expensive and readily available. The results were published in the online technical journal “Scientific Reports”.

The starting point for IWM researchers Wolfgang Körner, Georg Krugel, and Christian Elsässer was a neodymium-iron-nitrogen compound based on a type of...

Im Focus: Atomic precision: technologies for the next-but-one generation of microchips

In the Beyond EUV project, the Fraunhofer Institutes for Laser Technology ILT in Aachen and for Applied Optics and Precision Engineering IOF in Jena are developing key technologies for the manufacture of a new generation of microchips using EUV radiation at a wavelength of 6.7 nm. The resulting structures are barely thicker than single atoms, and they make it possible to produce extremely integrated circuits for such items as wearables or mind-controlled prosthetic limbs.

In 1965 Gordon Moore formulated the law that came to be named after him, which states that the complexity of integrated circuits doubles every one to two...

Im Focus: Researchers demonstrate size quantization of Dirac fermions in graphene

Characterization of high-quality material reveals important details relevant to next generation nanoelectronic devices

Quantum mechanics is the field of physics governing the behavior of things on atomic scales, where things work very differently from our everyday world.

Im Focus: Graphene: A quantum of current

When current comes in discrete packages: Viennese scientists unravel the quantum properties of the carbon material graphene

In 2010 the Nobel Prize in physics was awarded for the discovery of the exceptional material graphene, which consists of a single layer of carbon atoms...

Im Focus: Transparent - Flexible - Printable: Key technologies for tomorrow’s displays

The trend-forward world of display technology relies on innovative materials and novel approaches to steadily advance the visual experience, for example through higher pixel densities, better contrast, larger formats or user-friendler design. Fraunhofer ISC’s newly developed materials for optics and electronics now broaden the application potential of next generation displays. Learn about lower cost-effective wet-chemical printing procedures and the new materials at the Fraunhofer ISC booth # 1021 in North Hall D during the SID International Symposium on Information Display held from 22 to 27 May 2016 at San Francisco’s Moscone Center.

Economical processing

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Networking 4.0: International Laser Technology Congress AKL’16 Shows New Ways of Cooperations

24.05.2016 | Event News

Challenges of rural labor markets

20.05.2016 | Event News

International expert meeting “Health Business Connect” in France

19.05.2016 | Event News

 
Latest News

LZH shows the potential of the laser for industrial manufacturing at the LASYS 2016

25.05.2016 | Trade Fair News

Great apes communicate cooperatively

25.05.2016 | Life Sciences

Thermo-Optical Measuring method (TOM) could save several million tons of CO2 in coal-fired plants

25.05.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>