Cited by 154Mitochondrial Function and PathologyMagnesium in Health and DiseaseATP Synthase and ATPases Research

Mitochondrial Mg2+ homeostasis decides cellular energy metabolism and vulnerability to stress

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Yamanaka, Ryu, Tabata, Sho, Shindo, Yutaka, Hotta, Kohji, Suzuki, Koji, Soga, Tomoyoshi, Oka, Kotaro·2016·Scientific Reports

Abstract

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.

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Authors
Yamanaka, R., Tabata, S., Shindo, Y., Hotta, K., Suzuki, K., Soga, T., & Oka, K.
Affiliations
  • Keio University (JP)
  • Institute for Advanced Biosciences, Keio University (JP)
Corresponding author
Oka, Kotaro
Venue
Scientific Reports
Published
2016-07-26
Volume
6
Issue
1
Pages
30027-30027
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2502719111
Cited by
154
References
54
Citations by year
2026: 15 · 2025: 19 · 2024: 15 · 2023: 22 · 2022: 22 · 2021: 12 · 2020: 24 · 2019: 13 · 2018: 7 · 2017: 4
FWCI
4.16
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Ministry of Education, Culture, Sports, Science and Technology (2014?2018, S1411003)
  • Japan Society for the Promotion of Science (S1411003, 16K21361, 16H01751, 24240045)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Health Sciences › Nursing › Nutrition and Dietetics › Magnesium in Health and Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
Keywords
MRS2, cellular energy metabolism, ATP production, mitochondrial morphology, stress sensitivity, magnesium-dependent enzyme
MeSH terms
Biological Transport, Cell Physiological Phenomena, Energy Metabolism, HeLa Cells, Homeostasis, Humans, Magnesium, Mitochondria, Stress, Physiological, Mitochondrial Proteins, Cation Transport Proteins, RNA Interference, RNA, Small Interfering, Cell Line, Tumor, Membrane Potential, Mitochondrial

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