Research ArticleCell Biology

Ca2+ signals regulate mitochondrial metabolism by stimulating CREB-mediated expression of the mitochondrial Ca2+ uniporter gene MCU

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Science Signaling  03 Mar 2015:
Vol. 8, Issue 366, pp. ra23
DOI: 10.1126/scisignal.2005673

Maintaining mitochondrial calcium uptake

The calcium uniporter complex, which includes the protein MCU, mediates mitochondrial calcium uptake, a process that buffers excess cytosolic calcium and regulates mitochondrial metabolism. Shanmughapriya et al. examined mitochondrial calcium uptake and function in a B lymphocyte cell line deficient in one or more proteins necessary for mediating two types of calcium signals—IICR, calcium released from the endoplasmic reticulum through the calcium-permeable IP3 receptors, and SOCE, calcium influx through store-operated calcium channels. Without IICR or SOCE, the activity of the transcription factor CREB, which bound to the MCU promoter, and the expression and abundance of MCU were reduced, mitochondrial calcium uptake was compromised, and mitochondrial metabolism was altered. Cells deficient in IICR or SOCE lacked an oscillating basal calcium signal. Thus, IICR and SOCE control the capacity of mitochondria to uptake calcium and therefore regulate mitochondrial metabolism.

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