Details

Autor(en) / Beteiligte

• Vecellio Reane, Denis
• Vallese, Francesca
• Checchetto, Vanessa
• Acquasaliente, Laura
• Butera, Gaia
• De Filippis, Vincenzo
• Szabò, Ildikò
• Zanotti, Giuseppe
• Rizzuto, Rosario
• Raffaello, Anna

Titel

A MICU1 Splice Variant Confers High Sensitivity to the Mitochondrial Ca2+ Uptake Machinery of Skeletal Muscle

Ist Teil von

• Molecular cell, 2016-11, Vol.64 (4), p.760-773

Ort / Verlag

Elsevier Inc

Erscheinungsjahr

2016

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Skeletal muscle is a dynamic organ, characterized by an incredible ability to rapidly increase its rate of energy consumption to sustain activity. Muscle mitochondria provide most of the ATP required for contraction via oxidative phosphorylation. Here we found that skeletal muscle mitochondria express a unique MCU complex containing an alternative splice isoform of MICU1, MICU1.1, characterized by the addition of a micro-exon that is sufficient to greatly modify the properties of the MCU. Indeed, MICU1.1 binds Ca2+ one order of magnitude more efficiently than MICU1 and, when heterodimerized with MICU2, activates MCU current at lower Ca2+ concentrations than MICU1-MICU2 heterodimers. In skeletal muscle in vivo, MICU1.1 is required for sustained mitochondrial Ca2+ uptake and ATP production. These results highlight a novel mechanism of the molecular plasticity of the MCU Ca2+ uptake machinery that allows skeletal muscle mitochondria to be highly responsive to sarcoplasmic [Ca2+] responses. [Display omitted] •Skeletal muscle mitochondria express a unique MCU complex conserved in vertebrates•The complex prevalently contains the alternative splice isoform of MICU1, MICU1.1•MICU1.1-MICU2 heterodimers diminish the Ca2+ activation threshold of MCU•In skeletal muscle, MICU1.1 is required to amplify ATP supply for contraction Vecellio Reane et al. identify a unique skeletal muscle-specific mitochondrial Ca2+ uniporter complex containing an alternative splice isoform of MICU1, MICU1.1, that profoundly modifies the properties of mitochondrial Ca2+ uptake. MICU1.1 is required for providing sufficient levels of mitochondrial Ca2+ to sustain oxidative ATP production for resistance and strenuous exercise.