Cell cycle–dependent regulation of mitochondrial preprotein translocase

Mitochondria play central roles in cellular energy conversion, metabolism, and apoptosis. Mitochondria import more than 1000 different proteins from the cytosol. It is unknown if the mitochondrial protein import machinery is connected to the cell division cycle. We found that the cyclin-dependent kinase Cdk1 stimulated assembly of the main mitochondrial entry gate, the translocase of the outer membrane (TOM), in mitosis. The molecular mechanism involved phosphorylation of the cytosolic precursor of Tom6 by cyclin Clb3-activated Cdk1, leading to enhanced import of Tom6 into mitochondria. Tom6 phosphorylation promoted assembly of the protein import channel Tom40 and import of fusion proteins, thus stimulating the respiratory activity of mitochondria in mitosis. Tom6 phosphorylation provides a direct means for regulating mitochondrial biogenesis and activity in a cell cycle-specific manner. Cell division and mitochondrial protein import are directly linked by cyclin-dependent phosphorylation of a mitochondrial assembly factor. [Also see Perspective by Schulz and Rehling] Cross talk between mitochondria and mitosis Mitochondria, the power houses of the cell, contain their own genome. Nevertheless, the majority of their constituent proteins are encoded by nuclear genes and are translated in the cytosol. During the cell cycle, a cell needs to duplicate each of its constituent parts and organelles. Surprisingly, it has never been clear how or whether mitochondrial protein import is linked with the cell cycle. Harbauer et al. (see the Perspective by Schulz and Rehling) now show that one of the main conduits for mitochondrial protein import is directly regulated by phosphorylation during mitosis, and that this in turn promotes respiratory activity. Science, this issue p. 1109