Editors' ChoiceCalcium

Mitochondrial Uniporter Identified

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Science's STKE  27 Jan 2004:
Vol. 2004, Issue 217, pp. tw29-TW29
DOI: 10.1126/stke.2172004TW29

Kirichok et al. have identified a novel calcium (Ca2+)-selective ion channel as the elusive mitochondrial Ca2+ uniporter. Mitochondrial accumulation of Ca2+ shapes intracellular Ca2+ signals, regulates energy production, and has been implicated in cell death. The nature of the mitochondrial Ca2+ 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 Ca2+ current in whole mitoplasts that, like the mitochondrial Ca2+ uniporter, was inhibited by Ruthenium 360 and Ruthenium Red. This current, which the authors termed IMiCa, also showed the same cation selectivity and order of divalent cation permeability as the mitochondrial Ca2+ uniporter. The behavior of single MiCa channels analyzed by recording from inside-out mitoplast patches could account for the properties of the macroscopic IMiCa. MiCa was voltage-dependent, was highly selective for Ca2+, and carried sufficient Ca2+ current to account for mitochondrial Ca2+ uptake. Thus, the authors concluded that the MiCa channel functioned as the mitochondrial Ca2+ 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]

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