| First Author | Vecellio Reane D | Year | 2016 |
| Journal | Mol Cell | Volume | 64 |
| Issue | 4 | Pages | 760-773 |
| PubMed ID | 27818145 | Mgi Jnum | J:248720 |
| Mgi Id | MGI:6094378 | Doi | 10.1016/j.molcel.2016.10.001 |
| Citation | Vecellio Reane D, et al. (2016) A MICU1 Splice Variant Confers High Sensitivity to the Mitochondrial Ca(2+) Uptake Machinery of Skeletal Muscle. Mol Cell 64(4):760-773 |
| abstractText | 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 Ca(2+) one order of magnitude more efficiently than MICU1 and, when heterodimerized with MICU2, activates MCU current at lower Ca(2+) concentrations than MICU1-MICU2 heterodimers. In skeletal muscle in vivo, MICU1.1 is required for sustained mitochondrial Ca(2+) uptake and ATP production. These results highlight a novel mechanism of the molecular plasticity of the MCU Ca(2+) uptake machinery that allows skeletal muscle mitochondria to be highly responsive to sarcoplasmic [Ca(2+)] responses. |
