“…Several multi-component systems mediate the unfolding and translocation of protein substrates 12 , for example the SecYEG channel in translocation to the periplasm of prokaryotes, the Sec61αβγ channel in translocation to the ER of eukaryotes 5,13,14 , and TIM-TOM in translocation to the mitochondrial matrix 15 . The post-translational translocation of substrates in these systems includes 5,6 (i) targeting the protein substrate to the translocon; (ii) substrate unfolding; and (iii) translocation of the unfolded polypeptide chain through the translocon. While in some cases the process may require accessory proteins, such as chaperonins 2,16,17 , and the input of energy mediated by ATP, in others the presence of electrochemical gradients (approximately −180 mV in the mitochondrion) 18 , a membrane translocon, and a short, positively-charged targeting sequence at the N terminus of the substrate is enough for efficient targeting, unfolding and translocation 4,[19][20][21] .…”