Systems Biology | Rare Diseases | Common Diseases | Calcium
shim
shim
Calcium Uniporter  
shim
shim

Mitochondria uptake and buffer huge amounts of calcium via a channel called the "uniporter."  Calcium uptake into mitochondria activates the TCA cycle and is believed to serve as a key signal for coordinating mitochondrial ATP production with its utilization in the cytosol.  The uniporter has been studied for decades but its molecular composition has remained a complete mystery.  Our laboratory used comparative genomics and proteomics to discover all of the molecular components of the uniporter.  We also achieved the first in vivo reconstitution of this channel.  Detailed biophysical studies indicate that MICU1/MICU2 sense calcium in the inter membrane space to serve as an "on-off" switch for trans-membrane protein complex MCU/EMRE, the minimal components required for pore-activity.  Ongoing studies are aimed at a full molecular understanding of this channel complex in health and in disease.

 

 
 
   
   
   
   
   
   
 

 

     
   
     
     
    HMS MGH