Mitochondrial Mg(2+) Homeostasis Decides Cellular Energy Metabolism and Vulnerability to Stress

Overview

Journal Sci Rep

Specialty Science

Date 2016 Jul 27

PMID 27458051

Citations 68

Authors

Ryu Yamanaka

Sho Tabata

Yutaka Shindo

Kohji Hotta

Koji Suzuki

Tomoyoshi Soga

Kotaro Oka

Affiliations

Soon will be listed here.

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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