Contributors: Marchi, Saverio; Corricelli, Mariangela; Branchini, Alessio; Vitto, VERONICA ANGELA MARIA; Missiroli, Sonia; Morciano, Giampaolo; Perrone, Mariasole; Ferrarese, Mattia; Giorgi, Carlotta; Pinotti, Mirko; Galluzzi, Lorenzo; Kroemer, Guido; Pinton, Paolo
نبذة مختصرة : 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.
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