ISMB Seminar - Kostas Tokatlidis, University of Glasgow

We are delighted to present this week's ISMB Seminar Series speaker, Kostas Tokatlidis from the University of Glasgow, and their talk, "Unconventional protein import and oxidative folding sustain mitochondrial biogenesis and fitness".

Host:  Jerome Gouge

Mitochondria are critical organelles performing a variety of key functions in cells. Mitochondria biogenesis depends on the oxidative folding system, which retains imported proteins in the mitochondrial intermembrane space (IMS)  by adding disulfide bonds to them, to ensure their folding and retention in the IMS. All of the proteins of the IMS are nuclear-encoded and imported from the cytosol. The key players in the IMS oxidative folding system (also called the disulfide relay) are Mia40 ( a chaperone that recognises IMS-imported proteins and introduces the disulfides to them), and Erv1 (a FAD-oxidase that recycles Mia40 back to its oxidised state). We have dissected the structural and functional basis of this pathway, and how a class of specific targeting signals underpin this process. More recently we have found that cytosolic antioxidant proteins are dually localised to the IMS as well via unconventional import pathways.  These are the H2O2-thiol sensor Gpx3 and the reductive thioredoxin system consisting of thioredoxin and thioredoxin reductase. We will present data linking these systems to the optimal operation of folding and assembly in the IMS, which ensures mitochondria fitness particularly under stress conditions. These redox regulation systems in the IMS link mitochondrial biogenesis to the cell metabolic state and they serve as critical components of mitochondrial surveillance and quality control.