MICU2, a paralog of MICU1, resides within the mitochondrial uniporter complex to regulate calcium handling.

PLoS One
Authors
Keywords
Abstract

Mitochondrial calcium uptake is present in nearly all vertebrate tissues and is believed to be critical in shaping calcium signaling, regulating ATP synthesis and controlling cell death. Calcium uptake occurs through a channel called the uniporter that resides in the inner mitochondrial membrane. Recently, we used comparative genomics to identify MICU1 and MCU as the key regulatory and putative pore-forming subunits of this channel, respectively. Using bioinformatics, we now report that the human genome encodes two additional paralogs of MICU1, which we call MICU2 and MICU3, each of which likely arose by gene duplication and exhibits distinct patterns of organ expression. We demonstrate that MICU1 and MICU2 are expressed in HeLa and HEK293T cells, and provide multiple lines of biochemical evidence that MCU, MICU1 and MICU2 reside within a complex and cross-stabilize each other's protein expression in a cell-type dependent manner. Using in vivo RNAi technology to silence MICU1, MICU2 or both proteins in mouse liver, we observe an additive impairment in calcium handling without adversely impacting mitochondrial respiration or membrane potential. The results identify MICU2 as a new component of the uniporter complex that may contribute to the tissue-specific regulation of this channel.

Year of Publication
2013
Journal
PLoS One
Volume
8
Issue
2
Pages
e55785
Date Published
2013
ISSN
1932-6203
URL
DOI
10.1371/journal.pone.0055785
PubMed ID
23409044
PubMed Central ID
PMC3567112
Links
Grant list
R01 GM077465 / GM / NIGMS NIH HHS / United States
R24 DK080261 / DK / NIDDK NIH HHS / United States
DK080261 / DK / NIDDK NIH HHS / United States
GM0077465 / GM / NIGMS NIH HHS / United States