Rearrangement of MICU1 multimers for activation of MCU is solely controlled by cytosolic Ca2+

نویسندگان

  • Markus Waldeck-Weiermair
  • Roland Malli
  • Warisara Parichatikanond
  • Benjamin Gottschalk
  • Corina T. Madreiter-Sokolowski
  • Christiane Klec
  • Rene Rost
  • Wolfgang F. Graier
چکیده

Mitochondrial Ca(2+) uptake is a vital process that controls distinct cell and organelle functions. Mitochondrial calcium uptake 1 (MICU1) was identified as key regulator of the mitochondrial Ca(2+) uniporter (MCU) that together with the essential MCU regulator (EMRE) forms the mitochondrial Ca(2+) channel. However, mechanisms by which MICU1 controls MCU/EMRE activity to tune mitochondrial Ca(2+) signals remain ambiguous. Here we established a live-cell FRET approach and demonstrate that elevations of cytosolic Ca(2+) rearranges MICU1 multimers with an EC50 of 4.4 μM, resulting in activation of mitochondrial Ca(2+) uptake. MICU1 rearrangement essentially requires the EF-hand motifs and strictly correlates with the shape of cytosolic Ca(2+) rises. We further show that rearrangements of MICU1 multimers were independent of matrix Ca(2+) concentration, mitochondrial membrane potential, and expression levels of MCU and EMRE. Our experiments provide novel details about how MCU/EMRE is regulated by MICU1 and an original approach to investigate MCU/EMRE activation in intact cells.

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عنوان ژورنال:

دوره 5  شماره 

صفحات  -

تاریخ انتشار 2015