Navigation Links
Protein sensor for fatty acid buildup in mitochondria

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 nutrie nts. 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.


Source:St. Jude Children's Research Hospital

Related biology news :

1. Quantum Dots Research Leads to New Knowledge about Protein Binding in Plants
2. Protein discovery could unlock the secret to better TB treatment
3. Researchers Uncover Key Step In Manufacture of Memory Protein
4. An HIV Protein Plays a Surprising Role in Gene Activation
5. Protein Packages Found To Activate Genes; May Be What Regulates Development And Disease
6. New SARS Protein Linked To Important Cell Doorway
7. The Shapes Of Life: NIGMS Project Yields More Than 1,000 Protein Structures
8. PANTHER Protein Classification System Database 5.0
9. Duke Chemists Isolating Individual Molecules Of Toxic Protein In Alzheimers, Parkinsons Disease
10. Newly Discovered Compound Blocks Known Cancer-Causing Protein
11. UF Researchers Map Bacterial Proteins That Cause Tooth Loss
Post Your Comments:

(Date:10/29/2015)... YORK , Oct. 29, 2015 ... technology, announced a partnership with 2XU, a global ... to deliver a smart hat with advanced bio-sensing ... and other athletes to monitor key biometrics to ... the strategic partnership, the two companies will bring together ...
(Date:10/27/2015)... 2015 Synaptics Inc. (NASDAQ: SYNA ), the ... has adopted the Synaptics ® ClearPad ® ... its newest flagship smartphones, the Nexus 5X by LG ... --> --> Synaptics works closely ... collaboration in the joint development of next generation technologies. ...
(Date:10/26/2015)... -- Delta ID Inc., a company focused on bringing secure ... announced its ActiveIRIS® technology powers the iris recognition feature ... NTT DOCOMO, INC in Japan . ... include iris recognition technology, after a very successful introduction ... 2015, world,s first smartphone to have this capability. ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... 2015 Cepheid (NASDAQ: CPHD ) today ... following conference, and invited investors to participate via webcast. ...      Tuesday, December 1, 2015 at 11.00 a.m. Eastern Time ...      Tuesday, December 1, 2015 at 11.00 a.m. Eastern Time ... New York, NY      Tuesday, December 1, 2015 ...
(Date:11/24/2015)... (PRWEB) , ... November 24, 2015 , ... ... maintain healthy metabolism. But unless it is bound to proteins, copper is also ... Health (NIH), researchers at Worcester Polytechnic Institute (WPI) will conduct a systematic study ...
(Date:11/24/2015)... Inc., a worldwide provider of clinical research services headquartered in ... has set a new quarterly earnings record in Q3 of 2015.  ... Q3 of 2014 to Q3 of 2015.   ... the establishment of an Asia-Pacific office to ... and Mexico , with the establishment ...
(Date:11/24/2015)... ... ... The Academy of Model Aeronautics (AMA), led by its Executive Council, has ... Prix, to represent the First–Person View (FPV) racing community. , FPV racing has exploded ... of racing and several new model aviation pilots have joined the community because of ...
Breaking Biology Technology: