PMID- 27458051
OWN - NLM
STAT- MEDLINE
DCOM- 20180412
LR  - 20190111
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 6
DP  - 2016 Jul 26
TI  - Mitochondrial Mg(2+) homeostasis decides cellular energy metabolism and 
      vulnerability to stress.
PG  - 30027
LID - 10.1038/srep30027 [doi]
LID - 30027
AB  - Cellular energy production processes are composed of many Mg(2+) dependent 
      enzymatic reactions. In fact, dysregulation of Mg(2+) homeostasis is involved in 
      various cellular malfunctions and diseases. Recently, mitochondria, 
      energy-producing organelles, have been known as major intracellular Mg(2+) 
      stores. Several biological stimuli alter mitochondrial Mg(2+) concentration by 
      intracellular redistribution. However, in living cells, whether mitochondrial 
      Mg(2+) alteration affect cellular energy metabolism remains unclear. Mg(2+) 
      transporter of mitochondrial inner membrane MRS2 is an essential component of 
      mitochondrial Mg(2+) uptake system. Here, we comprehensively analyzed 
      intracellular Mg(2+) levels and energy metabolism in Mrs2 knockdown (KD) cells 
      using fluorescence imaging and metabolome analysis. Dysregulation of 
      mitochondrial Mg(2+) homeostasis disrupted ATP production via shift of 
      mitochondrial energy metabolism and morphology. Moreover, Mrs2 KD sensitized 
      cellular tolerance against cellular stress. These results indicate regulation of 
      mitochondrial Mg(2+) via MRS2 critically decides cellular energy status and cell 
      vulnerability via regulation of mitochondrial Mg(2+) level in response to 
      physiological stimuli.
FAU - Yamanaka, Ryu
AU  - Yamanaka R
AD  - Center for Biosciences and Informatics, School of Fundamental Science and 
      Technology Graduate School of Science and Technology, Keio University, Yokohama, 
      223-8522, Kanagawa, Japan.
FAU - Tabata, Sho
AU  - Tabata S
AD  - Institute for Advanced Biosciences, Keio University, Kakuganji, Tsuruoka, 
      Yamagata, 997-0052, Japan.
FAU - Shindo, Yutaka
AU  - Shindo Y
AD  - Center for Biosciences and Informatics, School of Fundamental Science and 
      Technology Graduate School of Science and Technology, Keio University, Yokohama, 
      223-8522, Kanagawa, Japan.
FAU - Hotta, Kohji
AU  - Hotta K
AD  - Center for Biosciences and Informatics, School of Fundamental Science and 
      Technology Graduate School of Science and Technology, Keio University, Yokohama, 
      223-8522, Kanagawa, Japan.
FAU - Suzuki, Koji
AU  - Suzuki K
AD  - Center for Science and Technology for Designing Functions, School of Integrated 
      Design Engineering, Graduate School of Science and Technology, Keio University, 
      Yokohama, Kanagawa, 223-8522, Japan.
FAU - Soga, Tomoyoshi
AU  - Soga T
AD  - Institute for Advanced Biosciences, Keio University, Kakuganji, Tsuruoka, 
      Yamagata, 997-0052, Japan.
FAU - Oka, Kotaro
AU  - Oka K
AD  - Center for Biosciences and Informatics, School of Fundamental Science and 
      Technology Graduate School of Science and Technology, Keio University, Yokohama, 
      223-8522, Kanagawa, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160726
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Cation Transport Proteins)
RN  - 0 (MRS2 protein, human)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - I38ZP9992A (Magnesium)
SB  - IM
MH  - Biological Transport/genetics
MH  - Cation Transport Proteins/*genetics
MH  - Cell Line, Tumor
MH  - Cell Physiological Phenomena
MH  - Energy Metabolism/*physiology
MH  - HeLa Cells
MH  - Homeostasis/physiology
MH  - Humans
MH  - Magnesium/*metabolism
MH  - Membrane Potential, Mitochondrial/genetics
MH  - Mitochondria/*metabolism
MH  - Mitochondrial Proteins/*genetics
MH  - RNA Interference
MH  - RNA, Small Interfering/genetics
MH  - Stress, Physiological/*genetics
PMC - PMC4960558
EDAT- 2016/07/28 06:00
MHDA- 2018/04/13 06:00
PMCR- 2016/07/26
CRDT- 2016/07/27 06:00
PHST- 2016/05/04 00:00 [received]
PHST- 2016/06/28 00:00 [accepted]
PHST- 2016/07/27 06:00 [entrez]
PHST- 2016/07/28 06:00 [pubmed]
PHST- 2018/04/13 06:00 [medline]
PHST- 2016/07/26 00:00 [pmc-release]
AID - srep30027 [pii]
AID - 10.1038/srep30027 [doi]
PST - epublish
SO  - Sci Rep. 2016 Jul 26;6:30027. doi: 10.1038/srep30027.