Mitochondrial Proteins Moonlighting in the Nucleus

Mitochondria function as cellular energy generators, producing the fuel required to drive biological processes. The response of cells to mitochondrial activity or dysfunction regulates their survival, growth, proliferation, and differentiation. Several proteins that contain mitochondrial-targeting sequences (MTS) also reside in the nucleus and there is increasing evidence that the nuclear translocation of mitochondrial proteins represents a novel pathway by which mitochondria signal their status to the cell. Here, we discuss the different mechanisms that control the dual mitochondrial and nuclear localisation of proteins and propose that these nuclear moonlighters represent a widespread regulatory circuit to maintain mitochondrial homeostasis.