The mitochondrial calcium uniporter complex: molecular components, structure and physiopathological implications

Abstract

Although it has long been known that mitochondria take up Ca2+, the molecular identities of the channels and transporters involved in this process were revealed only recently. Here, we discuss the recent work that has led to the characterization of the mitochondrial calcium uniporter complex, which includes the channel-forming subunit MCU (mitochondrial calcium uniporter) and its regulators MICU1, MICU2, MCUb, EMRE, MCUR1 and miR-25. We review not only the biochemical identities and structures of the proteins required for mitochondrial Ca2+ uptake but also their implications in different physiopathological contexts.

Figure 1

Ion fluxes are indicated by arrows. The lower magnification represents the different components of the uniporter complex. MCU Oligomerization at IMM forms a tetramer (shadowed subunits). MCUb is represented as the black shadowed subunit. SERCA, sarcoendoplasmic reticulum calcium transport ATPase; VDAC, voltage-dependent anion channel; TMD, transmembrane domain; RuR, Ruthenium Red. See text for further details.

Figure 2

Dynamic diagram showing Ca²⁺ changes in the different states of cytosolic Ca²⁺ upon MICU1 knock-down