Navigation Links
Sweet genes
Date:7/3/2014

Edmonton, July 3, 2014 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).


'/>"/>

Contact: Ross Neitz
rneitz@ualberta.ca
780-492-5986
University of Alberta Faculty of Medicine & Dentistry
Source:Eurekalert

Related biology news :

1. Sweet sweet straw
2. The sweetest calculator in the world
3. The future of sweet cherry in Australia
4. Childrens preferences for sweeter and saltier tastes are linked to each other
5. Nectar: A sweet reward from plants to attract pollinators
6. UT Austin engineer converts yeast cells into sweet crude biofuel
7. Are sweetpotato weevils differentially attracted to certain colors?
8. The economically valuable sweet-gum trees: Taxonomy and 9 new combinations
9. Targeting cancers sweet tooth
10. The brain cannot be fooled by artificial sweeteners
11. Carbonation alters the minds perception of sweetness
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/1/2016)... -- Today, the first day of American Heart Month, the ... first of its kind workplace health solution that leverages ... first application of Watson to ... Welltok will create a new offering that combines AHA,s ... on Welltok,s health optimization platform. The effort is intended ...
(Date:1/25/2016)... BELL, Pa. , Jan. 25, 2016   Unisys Corporation ... recognition system at John F. Kennedy (JFK) International Airport, ... Border Protection (CBP) identify imposters attempting to enter ... do not belong to them. pilot testing of ... out initially at three terminals at JFK during January 2016. ...
(Date:1/21/2016)... January 21, 2016 ... new market research report "Emotion Detection and Recognition Market by ... Tools (Facial Expression, Voice Recognition and Others), Services, ... forecast to 2020", published by MarketsandMarkets, the global ... reach USD 22.65 Billion by 2020, at a ...
Breaking Biology News(10 mins):
(Date:2/3/2016)... , Feb. 3, 2016 Ascendis Pharma ... company that applies its innovative TransCon technology to address ... at an upcoming investor conference.Event:2016 Leerink Partners Global Healthcare ... Date:  , Wednesday, February 10, 2016 Time:  , ... www.ascendispharma.com . --> An audio webcast of ...
(Date:2/3/2016)... BRUNSWICK, N.J. , Feb. 3, 2016 /PRNewswire-USNewswire/ ... grants totaling more than $1 million for researchers ... are working on health-related research that demonstrates exciting ... this round of funding for the New Jersey ... for faculty members at these educational institutions— Princeton ...
(Date:2/3/2016)... ... February 03, 2016 , ... ProMIS Neurosciences is currently ... specific to misfolded, propagating strains of Amyloid beta involved in Alzheimer’s disease. The ... Alzheimer’s. , Following on from the first misfolded Amyloid beta target announced on ...
(Date:2/3/2016)... ... February 03, 2016 , ... Resilinc ... summarizes and analyzes nearly 750 unique supply chain notifications and alerts generated by ... , Supply chain risk management practitioners subscribe to the EventWatch service to receive ...
Breaking Biology Technology: