Mitochondrial Ca2+ Uptake 1 (MICU1) and Mitochondrial Ca2+ Uniporter (MCU) Contribute to Metabolism-Secretion Coupling in Clonal Pancreatic β-Cells

Alam, Muhammad Rizwan; Groschner, Lukas N.; Parichatikanond, Warisara; Li, Kuo; Bondarenko, Alexander I.; Rost, René; Waldeck-Weiermair, Markus; Malli, Roland; Graier, Wolfgang F.

doi:10.1074/jbc.m112.392084

Cited by 127 publications

(107 citation statements)

References 41 publications

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“…As one might expect, this discovery has enabled a flurry of activity, as now gene-based tools are available for the study of mitochondrial calcium handling. Roles for the MCU have already been firmly established in insulin secretion, neuronal excitation, cell death, and other systems (Alam et al 2012;Mallilankaraman et al 2012;Shutov et al 2013;Tarasov et al 2013). …”

Section: The Calcium Uniportermentioning

confidence: 99%

Hallmarks of a new era in mitochondrial biochemistry

2013

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Stemming from the pioneering studies of bioenergetics in the 1950s, 1960s, and 1970s, mitochondria have become ingrained in the collective psyche of scientists as the “powerhouses” of the cell. While this remains a worthy moniker, more recent efforts have revealed that these organelles are home to a vast array of metabolic and signaling processes and possess a proteomic landscape that is both highly varied and largely uncharted. As mitochondrial dysfunction is increasingly being implicated in a spectrum of human diseases, it is imperative that we construct a more complete framework of these organelles by systematically defining the functions of their component parts. Powerful new approaches in biochemistry and systems biology are helping to fill in the gaps.

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Section: The Calcium Uniportermentioning

confidence: 99%

Hallmarks of a new era in mitochondrial biochemistry

2013

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“…MCU mediates glucosestimulated [Ca 2ϩ ] mito rise and second phase ATP/ADP increase (26). Knockdown of either MCU or MICU1 diminishes insulin secretion associated with defects in mitochondrial Ca 2ϩ uptake (32). Mice lacking MCU show a significant reduction of [Ca 2ϩ ] mito and Ca 2ϩ -stimulated oxygen consumption in muscle mitochondria, without changes in the basal respiration in embryonic fibroblasts (33).…”

mentioning

confidence: 99%

“…Several recent reports demonstrate the functional role of MCU in pancreatic ␤-cells (26,32). MCU mediates glucosestimulated [Ca 2ϩ ] mito rise and second phase ATP/ADP increase (26).…”

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confidence: 99%

Essential Role of Mitochondrial Ca2+ Uniporter in the Generation of Mitochondrial pH Gradient and Metabolism-Secretion Coupling in Insulin-releasing Cells

Quan

Nguyen

Choi

et al. 2015

Journal of Biological Chemistry

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Background: Mitochondrial Ca 2ϩ uptake affects energy metabolism and insulin secretion. Results: Knockdown of mitochondrial Ca 2ϩ uniporter decreases respiratory chain activity and mitochondrial pH gradient generation. Conclusion: Mitochondrial Ca 2ϩ uptake via uniporter is essential for oxidative phosphorylation and metabolism-secretion coupling. Significance: The present study identifies mechanisms of action and bioenergetic consequences of mitochondrial Ca 2ϩ transporters in insulin-releasing cells.

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“…24) A crucial role for MCU in glucose-induced [Ca 2+ ] m elevation in β-cells has been reported. 25) The involvement of MCU was investigated using the MCU selective inhibitor Ru360, which has greater membrane permeability than another MCU inhibitor, Ruthenium red. 26,27) ] m in β-cells remains unclear, and further investigation is needed.…”

Section: Effects Of 2-apb Andmentioning

confidence: 99%