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

• Published in: Scientific reports Vol. 6; no. 1
• Main Authors: Yamanaka, Ryu, Tabata, Sho, Shindo, Yutaka, Hotta, Kohji, Suzuki, Koji, Soga, Tomoyoshi, Oka, Kotaro
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26.07.2016; Nature Publishing Group
• Subjects: 14; 14/33; 14/34; 631/1647/320; 631/80/642/333/1465; 82/58; Humanities and Social Sciences; multidisciplinary; Science
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep30027

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.