| First Author | Marchi S | Year | 2019 |
| Journal | EMBO J | Volume | 38 |
| Issue | 2 | PubMed ID | 30504268 |
| Mgi Jnum | J:347326 | Mgi Id | MGI:7622130 |
| Doi | 10.15252/embj.201899435 | Citation | Marchi S, et al. (2019) Akt-mediated phosphorylation of MICU1 regulates mitochondrial Ca(2+) levels and tumor growth. EMBO J 38(2) |
| abstractText | Although mitochondria play a multifunctional role in cancer progression and Ca(2+) signaling is remodeled in a wide variety of tumors, the underlying mechanisms that link mitochondrial Ca(2+) homeostasis with malignant tumor formation and growth remain elusive. Here, we show that phosphorylation at the N-terminal region of the mitochondrial calcium uniporter (MCU) regulatory subunit MICU1 leads to a notable increase in the basal mitochondrial Ca(2+) levels. A pool of active Akt in the mitochondria is responsible for MICU1 phosphorylation, and mitochondrion-targeted Akt strongly regulates the mitochondrial Ca(2+) content. The Akt-mediated phosphorylation impairs MICU1 processing and stability, culminating in reactive oxygen species (ROS) production and tumor progression. Thus, our data reveal the crucial role of the Akt-MICU1 axis in cancer and underscore the strategic importance of the association between aberrant mitochondrial Ca(2+) levels and tumor development. |
