Navigation Links
What keeps a cell's energy source going

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
University of Pennsylvania School of Medicine

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:
Related Image:
What keeps a cell's energy source going
(Date:11/25/2015)... ... , ... According to an article published November 10th by The ... as a breakthrough for performing hernia repairs. The article explains that the biggest advantage ... it can greatly reduce the pain that a patient might otherwise experience after a ...
(Date:11/25/2015)... ... 25, 2015 , ... Dental professionals who would like to become more proficient ... attend Dr. Mark Iacobelli’s Advanced Implant Mentoring (AIM) CE course. Courses will be held ... the co-founders of Advanced Implant Mentoring (AIM), Dr. Iacobelli and Dr. D’Orazio are proud ...
(Date:11/25/2015)... ... November 25, 2015 , ... ... and athletic programs, launches new Wimbledon Athletics Facebook page to educate ... athletes for unsuspected cardiac abnormalities. About 2,000 people under the age of 25 ...
(Date:11/25/2015)... ... ... On November 23rd 2015 Cozy Products, a division of Bird-X ... Products explains what this means for business moving forward. , The Tri Lite heater ... model: to sell personal heaters that reduce energy consumption, are economical and keep people ...
(Date:11/25/2015)... , ... November 25, 2015 , ... ... double board certified facial plastic surgeon specializing in both surgical and non-surgical treatments, ... The Skin Spa at Hobgood Facial Plastic Surgery. , Highly trained and ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... November 26, 2015 ... addition of the  "2016 Future Horizons ... Cell Surface Marker Testing Market: Supplier ... to their offering.  --> ... of the  "2016 Future Horizons and ...
(Date:11/25/2015)... , Nov. 25, 2015  Linden Care, LLC, a ... treatment outcomes for patients suffering from chronic pain, said ... a Temporary Restraining Order (TRO) enjoining Express Scripts from ... companies. --> --> ... of its legal options. --> ...
(Date:11/25/2015)... AVIV, Israel , November 25, 2015 ... (NASDAQ: KTOV ) (TASE: KTOV), a biopharmaceutical company ... simultaneous treatment of various clinical conditions, today announced the ... 3,158,900 American Depository Shares ( ADSs ), each representing ... purchase up to 3,158,900 ADSs. The ADSs and warrants ...
Breaking Medicine Technology: