Mitochondrial Mg2+ homeostasis decides cellular energy metabolism and vulnerability to stress
Open accessAbstract
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)
- PMC
- PMC4960558
- 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
- gold
- doi.org
- 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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