Abstract 091: Mitochondrial Calcium Currents Are Conducted By A Pore Encoded By The MCU Gene.
Mitochondrial uptake of calcium (Ca2+) in cardiomyocytes is thought to regulate cell survival and match ATP production to energetic demands. Of multiple pathways allowing such entry, the mitochondrial Ca2+ uniporter is a highly Ca2+-selective channel encoded by several recently-discovered genes. However, which of these several genes encodes the pore-forming subunit of the channel remains an open question. Using whole-mitoplast voltage-clamping, we show that RNAi-mediated knockdown of the mitochondrial calcium uniporter (MCU) gene reduces the uniporter current (IMiCa), whereas overexpression increases it. Mutations in the putative pore domain alter key features of IMiCa, such as its strong affinity for ruthenium red, a classic uniporter blocker. These analyses demonstrate that MCU encodes the pore-forming subunit of the uniporter channel.
- © 2013 by American Heart Association, Inc.