Mitochondrial Uniporter Identified

Kirichok et al . have identified a novel calcium (Ca 2+ )-selective ion channel as the elusive mitochondrial Ca 2+ uniporter. Mitochondrial accumulation of Ca 2+ shapes intracellular Ca 2+ signals, regulates energy production, and has been implicated in cell death. The nature of the mitochondrial Ca 2+ uniporter that enables this uptake, however, has been unclear. Kirichok et al . patch-clamped "mitoplasts" (vesicles derived from the inner mitochondrial membranes) from COS-7 cells and measured an inwardly rectifying Ca 2+ current in whole mitoplasts that, like the mitochondrial Ca 2+ uniporter, was inhibited by Ruthenium 360 and Ruthenium Red. This current, which the authors termed I MiCa , also showed the same cation selectivity and order of divalent cation permeability as the mitochondrial Ca 2+ uniporter. The behavior of single MiCa channels analyzed by recording from inside-out mitoplast patches could account for the properties of the macroscopic I MiCa . MiCa was voltage-dependent, was highly selective for Ca 2+ , and carried sufficient Ca 2+ current to account for mitochondrial Ca 2+ uptake. Thus, the authors concluded that the MiCa channel functioned as the mitochondrial Ca 2+ uniporter. Y. Kirichok, G. Krapivinsky, D. E. Clapham, The mitochondrial calcium uniporter is a highly selective ion channel. Nature 427 , 360-364 (2004). [Online Journal]