No abstract

The biogenesis of mitochondria requires the import of hundreds of precursor proteins. These proteins are transported post-translationally with the help of chaperones, meaning that the overproduction of mitochondrial proteins or the limited availability of chaperones can lead to the accumulation of cytosolic precursor proteins. This imposes a severe challenge to cytosolic proteostasis, and triggers a specific transcription program, called the mitoprotein-induced stress response, which activates the proteasome system. This coincides with the repression of mitochondrial proteins, including many proteins of the intermembrane space (IMS). In contrast, herein we report that the so far uncharacterized IMS protein Mix23 is considerably up-regulated when mitochondrial import is perturbed. Mix23 is evolutionarily conserved and a homolog of the human coiled-coil domain containing 58, CCDC58. We found that, like the subunits of the proteasome, Mix23 is under control of the transcription factor Rpn4. It is imported into mitochondria by the mitochondrial disulfide relay. Mix23 is critical for the efficient import of proteins into the mitochondrial matrix particularly if the function of the TIM23 translocase is compromised such as in temperature-sensitive mutants of Tim17. Our observations identify Mix23 as a novel regulator or stabilizer of the mitochondrial protein import machinery that is specifically upregulated upon mitoprotein-induced stress conditions.

No abstract

Tandem fluorescent protein timers are elegant tools to determine proteolytic stabilities of cytosolic proteins with high spatial and temporal resolution. In a new study published in BMC Biology, Kowalski et al. fused timers to precursors of proteins of the mitochondrial intermembrane space and found that they are under surveillance of the ubiquitin-proteasome system. Ubiquitination at lysine residues of these precursors directly inhibits their translocation into the intermembrane space and targets them for proteasomal degradation.

No abstract