Navigation Links
What keeps a cell's energy source going
Date:11/27/2012

PHILADELPHIA Most healthy cells rely on a complicated process to produce the fuel ATP. Knowing how ATP is produced by the cell's energy storehouse the mitochondria -- is important for understanding a cell's normal state, as well as what happens when things go wrong, for example in cancer, cardiovascular disease, neurodegeneration, and many rare disorders of the mitochondria.

Two years ago, Kevin Foskett, PhD, professor of Physiology at the Perelman School of Medicine, University of Pennsylvania, and colleagues discovered that fundamental control of ATP production is an ongoing shuttle of calcium to the mitochondria from another cell compartment. They found that mitochondria rely on this transfer to make enough ATP to support normal cell metabolism.

Foskett's lab and the lab of colleague Muniswamy Madesh, PhD, at Temple University, discovered last month an essential mechanism that regulates the flow of calcium into mitochondria, described in the October 26 issue of Cell. They found that the mitochondrial protein MICU1 is required to establish the proper level of calcium uptake under normal conditions.

In a new paper out this week in Nature Cell Biology, the same Penn-Temple team describe a new protein and its function. Like MICU1, this new protein, MCUR1, interacts physically with MCU, the uniporter calcium ion channel within the mitochondria. Calcium uptake is driven by a voltage across the inner mitochondrial membrane and mediated by the calcium-selective ion channel called the uniporter.

"But this newly described protein, MCUR1, has the opposite role as MICU1," notes Foskett. "It seems to be a subunit that, together with MCU, is required for a functional uniporter calcium channel."

Many cell plasma membrane ion channels also have subunits that are required for those channels to work. Before this paper, there was no realization that this mitochondrial channel, MCU, did as well.

Maintaining the correct levels of calcium in the mitochondria plays an important role in cellular physiology: Calcium flux across the inner mitochondrial membrane regulates cell energy production and activation of cell-death pathways, for example. In MICU1's absence mitochondria become overloaded with calcium, generating excessive amounts of reactive oxygen molecules and eventually cell death. In contrast, in the absence of MCUR1, mitochondria cannot take up enough calcium. This also has detrimental effects: the cells cannot make enough ATP and they activate autophagy, a mechanism in which cells "eat themselves" to provide sufficient nutrients for survival

Both papers deal with the function of the uniporter, the calcium channel in the inner membrane of mitochondria that lets calcium get into the mitochondrial matrix where it can do good things like promote ATP synthesis and healthy bioenergetics, or bad things, like mitochondrial-mediated cell death, apoptosis and necrosis.

Because of these two papers, the uniporter is now recognized as a channel complex, containing -- at least -- MCU, MCUR1 and MICU1. Since the uniporter can be a therapeutic target is reperfusion injury, ischemic injury, and programmed cell death, MCUR1 and its interaction with MCU are now targets for drug development.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

Related medicine news :

1. A fish a day keeps the doctor away?
2. Playing Several Sports Keeps Kids Slimmer: Study
3. Weight loss today keeps the doctor away
4. Cost Keeps Many Americans From Good Dental Care: Report
5. Oxytocin keeps flirting folks at arms length
6. New drug prevents spread of human prostate cancer cells
7. Tiny hitchhikers attack cancer cells
8. To prevent leukemias dreaded return, go for the stem cells
9. Scientists identify major source of cells defense against oxidative stress
10. Therapy exploits addiction of leukemia cells
11. IBN discovers human neural stem cells with tumor targeting ability
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
What keeps a cell's energy source going
(Date:10/13/2017)... ... ... Journey: From the Mountains to the Mission Field”: the story of a missionary couple ... From the Mountains to the Mission Field” is the creation of published author, Carole ... and currently teaches a class of ladies at her church, which she has taught ...
(Date:10/12/2017)... ... October 12, 2017 , ... CitiDent ... sleep apnea using cutting-edge Oventus O2Vent technology. As many as 18 million ... by frequent cessation in breathing. Oral appliances can offer significant relief to about ...
(Date:10/12/2017)... , ... October 12, 2017 , ... IsoComforter, Inc. ( ... announced today the introduction of an innovative new design of the shoulder pad. ... you get maximum comfort while controlling your pain while using cold therapy. By utilizing ...
(Date:10/12/2017)... Rockville, Maryland (PRWEB) , ... October 12, 2017 ... ... a magnetic drug delivery system that we intend to develop to enable prevention ... regimens can lead to severe hearing loss, especially in pediatric patients. For cisplatin, ...
(Date:10/12/2017)... , ... October 12, 2017 , ... Leading pediatric oncology ... in Washington, D.C., for the 49th Congress of the International Society of Paediatric ... President of the Center for Cancer and Blood Disorders at Children’s National, ...
Breaking Medicine News(10 mins):
(Date:10/11/2017)... 2017  Hill-Rom Holdings, Inc. ("Hill-Rom") (NYSE: HRC), today ... Las Piedras, Puerto Rico , where ... Following a comprehensive ... minor structural damage, temporary loss of power and minimal ... completed, manufacturing operations have resumed, and the company expects ...
(Date:10/10/2017)... EXTON, Pa. , Oct. 10, 2017   ... leader in innovative solutions for injectable drug administration, today ... of West,s ID Adapter for improving the intradermal administration ... the Fourth Skin Vaccination Summit in May 2017 by ... Team Lead, Polio Department, World Health Organization (WHO), and ...
(Date:10/5/2017)... Ill. , Oct. 5, 2017  In ... Association of Oral and Maxillofacial Surgeons (AAOMS) released ... opioids – to be used as a first-line ... pain. Recognizing ... the AAOMS White Paper "Opioid Prescribing: Acute and ...
Breaking Medicine Technology: