Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein sensor for fatty acid buildup in mitochondria

16.02.2007
St. Jude study shows PanK2 enzyme within mitochondria is triggered by the first step in fatty acid breakdown

Just as homes have smoke detectors, cells have an enzyme that responds to a buildup of fatty acids by triggering the production of a key molecule in the biochemical pathway that breaks down these fatty acids, according to investigators at St. Jude Children's Research Hospital. This breakdown of fatty acids, in turn, provides the cell energy while reducing the chance that excess fatty acids will accumulate.

The St. Jude discovery explains how the fatty acid-sensing enzyme PanK2 tailors production of this key molecule, coenzyme A (CoA), to the cell's energy demands. Understanding PanK2 function is also important because mutations in this enzyme cause an inherited neurodegenerative disease. A report on the discovery appears in the online pre-publication issue of Proceedings of the National Academy of Sciences (PNAS).

"The results of this study show how and where a critical biochemical pathway for fatty acid breakdown is controlled by a specific enzyme," said Charles Rock, Ph.D., a member of the Infectious Diseases department at St. Jude. "It offers an explanation of why the absence of this enzyme can cause mitochondrial malfunction." Rock is a co-author of the PNAS paper.

The researchers showed that PanK2, is suppressed by CoA—the molecule this enzyme triggers the cell to make. CoA normally binds tightly to PanK2, shutting it down. When a buildup of fatty acids occurs in the cell, a molecule called carnitine shuttles them into the mitochondria. This combination of a fatty acid and carnitine, called acylcarnitine, liberates PanK2 from the bondage of CoA. Once free, PanK2 resumes its job of initiating the production of more CoA, which is needed for the breakdown of fatty acids—a process called beta-oxidation.

The St. Jude team demonstrated that PanK2 does its job of responding to increasing levels of fatty acids within a structure called the mitochondrion. Mitochondria are bags of enzymes in the cell that extract energy from nutrients. Most of the cell's energy-rich molecules called ATP are made in the mitochondria, and these ATP molecules serve as the "currency" with which the cell can "buy" all of the biochemical reactions that keep the cell alive and performing its functions. Virtually all cells have mitochondria, and disruption of their function can cause a variety of diseases.

"Our study showed the connection between the location of PanK2 in the mitochondria and its role in as a sensor of energy demand," said Yong-Mei Zhang, Ph.D., a researcher in the Infectious Diseases department at St. Jude and the report's senior author. "This is an ideal location for PanK2 because it can detect acylcarnitine as it enters the mitochondrion."

The importance of PanK2 is especially evident in individuals who have mutations in the PANK2 gene that give rise to PanK-associated neurodegeneration (PKAN), an inherited disease in which patients have intellectual impairment and difficulty in walking and speaking.

"The new understanding of PanK2 activity and its location in the cell suggests a potential treatment strategy for PKAN," said Roberta Leonardi, Ph.D., a postdoctoral fellow in the St. Jude Infectious Diseases department and first author of the PNAS article. "For example, reducing the level of fat in the diet and taking carnitine supplements might help PKAN patients cope with this debilitating disease."

"One of our challenges is how to develop an animal model of this disease that we can use to determine if reduced dietary fat and carnitine supplements offer hope in the treatment of PKAN in humans," said Suzanne Jackowski, Ph.D., a member of the Infectious Diseases department at St. Jude and a co-author of the report.

Summer Freeman | EurekAlert!
Further information:
http://www.stjude.org

Further reports about: CoA Infectious Diseases PKAN PanK2 buildup carnitine mitochondria

More articles from Life Sciences:

nachricht Molecular microscopy illuminates molecular motor motion
26.07.2017 | Penn State

nachricht New virus discovered in migratory bird in Rio Grande do Sul, Brazil
26.07.2017 | Fundação de Amparo à Pesquisa do Estado de São Paulo

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

 
Latest News

CCNY physicists master unexplored electron property

26.07.2017 | Physics and Astronomy

Molecular microscopy illuminates molecular motor motion

26.07.2017 | Life Sciences

Large-Mouthed Fish Was Top Predator After Mass Extinction

26.07.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>