Abstract
Recently identified core proteins (MICU1, MCU, EMRE) forming the mitochondrial Ca2+ uniporter complex propelled investigations into its physiological workings. Here, we apply structured illumination microscopy to visualize and localize these proteins in living cells. Our data show that MICU1 localizes at the inner boundary membrane (IBM) due to electrostatic interaction of its polybasic domain. Moreover, this exclusive localization of MICU1 is important for the stability of cristae junctions (CJ), cytochrome c release and mitochondrial membrane potential. In contrast to MICU1, MCU and EMRE are homogeneously distributed at the inner mitochondrial membrane under resting conditions. However, upon Ca2+ elevation MCU and EMRE dynamically accumulate at the IBM in a MICU1-dependent manner. Eventually, our findings unveil an essential function of MICU1 in CJ stabilization and provide mechanistic insights of how sophistically MICU1 controls the MCU-Complex while maintaining the structural mitochondrial membrane framework.
Highlights
Identified core proteins (MICU1, MCU, EMRE) forming the mitochondrial Ca2+ uniporter complex propelled investigations into its physiological workings
Super-resolution images under resting conditions and after stimulation with histamine were acquired. These experiments show that MICU1 exclusively localizes to the IBM15, and that this distribution does not change upon histamine stimulation (Fig. 1a, b)
We utilized live-cell structured illumination microscopy (SIM) and combined it with transmission electron microscopy[34] and newly designed tools for spatial Ca2+ measurements to investigate the spatial dynamics of the MCU-Complex and the organization of the IMM under resting conditions and upon cell stimulation
Summary
Identified core proteins (MICU1, MCU, EMRE) forming the mitochondrial Ca2+ uniporter complex propelled investigations into its physiological workings. Our data show that MICU1 localizes at the inner boundary membrane (IBM) due to electrostatic interaction of its polybasic domain. This exclusive localization of MICU1 is important for the stability of cristae junctions (CJ), cytochrome c release and mitochondrial membrane potential. Biochemical signals in and out of mitochondria have to pass the outer (OMM) and inner (IMM) mitochondrial membrane In this context, Ca2+ transport has been studied due to its importance for metabolic activity or initiating cell death programs[1]. We exploit super-resolution structured illumination microscopy (SIM), electron microscopy and newly designed submitochondrial Ca2+ recordings to identify sub-mitochondrial distribution, dynamics, and localization-derived functions of MICU1 and MCU-Complex components under resting conditions and upon Ca2+ mobilization. Our data present MICU1 as multifunctional regulator of an on-demand assembly of the MCUComplex and mediator of Ca2+ signaling to the cristae
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