Tuning the mitochondrial protein import machinery by reversible phosphorylation: from metabolic switches to cell cycle regulation

Abstract

The almost entire mitochondrial proteome is build up by the import of nuclear encoded precursor proteins from the cytosol. This process is mediated by several sophisticated protein machineries in the outer and inner membrane that translocate and — dependent on the presence of a certain type of signal sequence within the precursors — sort the preproteins to the respective suborganellar destination. The mitochondrial protein import machinery has been considered for long time to be constitutively active and work in a rather static manner. However, recent studies have revealed that the import machinery is the target of several cytosolic and mitochondrial protein kinases implying a tight connection of mitochondrial protein biogenesis and cellular signaling cascades. In this mini review we highlight how the translocase of the outer membrane (TOM) as the central protein entry gate into the organelle is modulated by reversible phosphorylation. This allows a dynamic regulation of TOM biogenesis and function, which is important to adapt the organellar proteome to changing cellular demands upon metabolic switches or to link protein import activity to certain stages of the cell cycle.