On the other side of the membrane: A new role for a luminal protein in the cytoplasm

Proteins annotated as localizing inside membrane-bound organelles are accepted as residing there. Thus, encountering a mitochondrial cytochrome in the cytoplasm would be unexpected. Yet, a mitochondrial cytochrome does relocalize to the cytoplasm during apoptotic cell death. In fact, a growing list of annotated luminal proteins has demonstrable cytoplasmic functions. It is with this perspective of bi-compartmental proteins that I encourage you to read the new study from Zhu and Fu in this issue of The FEBS Journal. The authors investigate how stress inside the ER lumen influences cytoplasmic energy regulation and uncover a surprising mechanism in fission yeast.