Navigation Links
Hopkins researchers discover genetic switch that turns off an oxygen-poor cell's combustion engine

hypoxia, the mitochondrion produces reactive oxygen species that threaten the life of the cell.

"But our discovery clearly shows that hypoxia doesn't simply trigger a passive shutdown of the mitochondrion," said Dang. "Instead, HIF-1 acts as a genetic switch to actively shut down mitochondrial function and prevent the production of reactive oxygen species."

The Hopkins team demonstrated that HIF-1 shuts down the TCA cycle by preventing an enzyme called PDH from converting pyruvate made by glycolysis into acetyl CoA. Specifically, HIF-1 blocks the ability of PDH to make this conversion. HIF-1 does this by activating a protein called PDK, which binds to PDH and prevents it from performing this critical task. This starves the TCA cycle of acetyl CoA and shuts it down.

The Hopkins researchers made their discovery using mouse embryo fibroblast (MEF) cells that were genetically altered to lack HIF-1. When the investigators exposed these so-called HIF-1 null MEFs to hypoxic conditions, the cells were unable to activate PDK to block mitochondrial function. This showed that HIF-1 is required to activate PDK.

The team then genetically engineered HIF-1 null MEFs and forced PDK to work-even in the absence of the HIF-1 gene. The hypoxic cells once again accelerated glycolysis and produced increased amounts of ATP; and with the PDK forced to work, the cells were also able to shut down the TCA cycle. This showed that PDK is the protein activated by HIF-1 to prevent the mitochondrion from producing ROS.

The other authors of this paper include Jung-whan Kim, Irina Tchernyshyov and Gregg L. Semenza, who discovered HIF-1 a decade ago.


'"/>

Source:Johns Hopkins Medical Institutions


Page: 1 2 3

Related biology news :

1. Hopkins AIDS experts issue warning about global efforts to provide drug therapies
2. Hopkins scientists uncover tags that force proteins to cell surface
3. Johns Hopkins flu expert calls for mandatory vaccination of health care workers
4. Whole-genome study at Johns Hopkins reveals a new gene associated with abnormal heart rhythm
5. Hopkins study suggests commercially available antibiotic may help fight dementia in HIV patients
6. Johns Hopkins lab scientists tame overactive CF protein
7. Hopkins researchers develop new tool to watch real-time chemical activity in cells
8. Hopkins scientists show hallucinogen in mushrooms creates universal mystical experience
9. Hopkins researchers discover how brain protein might control memory
10. Hopkins scientists link immune response to ghost parasites and severely congested sinuses
11. NYU researchers simulate molecular biological clock
Post Your Comments:
(Date:5/17/2013)... (May 18, 2013) The AGA Research Foundation announced ... the relationship between the gut microbiota, one of today,s ... disease. , The AGA Research Awards Panel selected ... Massachusetts General Hospital and Harvard Medical School, Boston, as ... Dr. Chan will receive $25,000 of funding, commencing in ...
(Date:5/17/2013)... the interaction of a group of proteins in the ... identified a new target that could increase cell survival. ... School of Biochemistry and published in the EMBO ... eventually lead to new therapies for stroke and other ... by the team which identified a protein, known as ...
(Date:5/17/2013)... Bethesda, MD The Federation of American Societies for ... of National Institutes of Health (NIH) funding trends highlighting ... to support critical research. The FASEB analysis follows a ... Francis Collins, MD, PhD, who testified that the $1.6 ... to sequestration is "having a substantial impact on the ...
Breaking Biology News(10 mins):New gut microbiome research to explore red meat -- colorectal cancer pathway 2SUMO wrestling cells reveal new protective mechanism target for stroke 2
... 10, 2009)Attempts to treat critical limb ischemia in ... are still thwarted by restenosis (the re-narrowing of ... stenting), the need for repeat treatments and the ... death (gangrene) and amputation. Interventional radiologists have been ...
... Detects Faces in Motion, Matches with Watch-list ... Lithuania, March 9 Neurotechnology, a provider ... the availability of VeriLook Surveillance SDK, a ... using live video streams from high-resolution digital ...
... be tough, but scientists have found a Yellowstone National ... simple one-celled algae called Cyanidioschyzon -- thrives ... occurs naturally around hot springs, said Tim McDermott, professor ... at Montana State University. Cyanidioschyzon could ...
Cached Biology News:Promising 3-year data: Saving limbs with drug-eluting stents 2Promising 3-year data: Saving limbs with drug-eluting stents 3VeriLook Surveillance SDK Provides Real-Time Face Identification Using Video Surveillance Cameras 2VeriLook Surveillance SDK Provides Real-Time Face Identification Using Video Surveillance Cameras 3Montana State team finds Yellowstone alga that detoxifies arsenic 2Montana State team finds Yellowstone alga that detoxifies arsenic 3
(Date:5/21/2013)... Branchburg, NJ (PRWEB) May 21, 2013 ... enhancement industry, has appointed Dale Braddy to Southeastern USA ... proactively bolster its sales muscle in the Southeast. ... a food ingredient brokerage and supplier to food processors ... past 13 years in the food industry and has ...
(Date:5/21/2013)... As the R&D sector becomes ... the industry to deliver better products, faster. Collaborations ... companies often means turning big ideas into reality, ... collaboration with Sensidose AB and Recipharm, is one ... to market sooner. The partnership resulted in the ...
(Date:5/21/2013)... May 21, 2013  Synthetic Biologics, Inc. (NYSE MKT: SYN), ... of serious infectious diseases, announced today that Jeffrey ... Annual Marcum LLP MicroCap Conference on Thursday, May 30, ... the Grand Hyatt Hotel. Mr. Riley is scheduled to present ... of Synthetic Biologics, presentation can be accessed by logging onto ...
(Date:5/21/2013)... NANONEX CORPORATION, a pioneer and leading company ... successful delivery and installation of a new nanoimprint ... major Japanese manufacturing company. , ... lithography tool that has the ability to process ... types. Based on Nanonex inventions and proprietary technologies, ...
Breaking Biology Technology:The Development of an Innovative Microtablet Dosage Form, a Success Story: Live Webinar Hosted by Xtalks 2Synthetic Biologics to Present at the 2nd Annual Marcum LLP MicroCap Conference 2Nanonex Announces the Shipment and Installation of an Innovative Nanoimprint Lithography System for Fully Automated Manufacturing 2
... BOULDER, Colo., and IPSWICH, Mass., July 27, ... Biolabs, Inc. (NEB) announce today that they ... whereby SomaLogic will provide specific SOMAmers as ... and future NEB nucleic acid amplification and ...
... July 27, 2011 Cadence Pharmaceuticals, Inc. (NASDAQ: ... and commercializing proprietary products principally for use in the hospital ... ended June 30, 2011 financial results on Wednesday, August 3, ... call and live webcast to discuss the financial results on ...
... Keryx Biopharmaceuticals, Inc. (Nasdaq: KERX ) today ... registration trial of KRX-0401 (perifosine) for the treatment of ... over 430 randomized patients, is being conducted pursuant to ... Drug Administration (FDA) and with Fast-Track Designation.  Perifosine is ...
Cached Biology Technology:Agreement Between SomaLogic and New England Biolabs Enables the Use of SOMAmer Technology for the Optimization of Multiple PCR Products 2Keryx Biopharmaceuticals Announces Completion of Patient Enrollment in KRX-0401 (Perifosine) Phase 3 Refractory Advanced Colorectal Cancer Study 2Keryx Biopharmaceuticals Announces Completion of Patient Enrollment in KRX-0401 (Perifosine) Phase 3 Refractory Advanced Colorectal Cancer Study 3Keryx Biopharmaceuticals Announces Completion of Patient Enrollment in KRX-0401 (Perifosine) Phase 3 Refractory Advanced Colorectal Cancer Study 4Keryx Biopharmaceuticals Announces Completion of Patient Enrollment in KRX-0401 (Perifosine) Phase 3 Refractory Advanced Colorectal Cancer Study 5