Structure and Function of the N-terminal Domain of the Human Mitochondrial Calcium Uniporter

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2015 Sep 6

PMID 26341627

Citations 53

Authors

Youngjin Lee

Choon Kee Min

Tae Gyun Kim

Hong Ki Song

Yunki Lim

Dongwook Kim

Kahee Shin

Moonkyung Kang

Jung Youn Kang

Hyung-Seop Youn

Jung-Gyu Lee

Jun Yop An

Kyoung Ryoung Park

Jia Jia Lim

Ji Hun Kim

Ji Hye Kim

Zee Yong Park

Yeon-Soo Kim

Jimin Wang

Do Han Kim

Soo Hyun Eom

Affiliations

Soon will be listed here.

Abstract

The mitochondrial calcium uniporter (MCU) is responsible for mitochondrial calcium uptake and homeostasis. It is also a target for the regulation of cellular anti-/pro-apoptosis and necrosis by several oncogenes and tumour suppressors. Herein, we report the crystal structure of the MCU N-terminal domain (NTD) at a resolution of 1.50 Å in a novel fold and the S92A MCU mutant at 2.75 Å resolution; the residue S92 is a predicted CaMKII phosphorylation site. The assembly of the mitochondrial calcium uniporter complex (uniplex) and the interaction with the MCU regulators such as the mitochondrial calcium uptake-1 and mitochondrial calcium uptake-2 proteins (MICU1 and MICU2) are not affected by the deletion of MCU NTD. However, the expression of the S92A mutant or a NTD deletion mutant failed to restore mitochondrial Ca(2+) uptake in a stable MCU knockdown HeLa cell line and exerted dominant-negative effects in the wild-type MCU-expressing cell line. These results suggest that the NTD of MCU is essential for the modulation of MCU function, although it does not affect the uniplex formation.

Citing Articles

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