Proteins that carry dual targeting signals can act as tethers between peroxisomes and partner organelles

by Elena Bittner, Thorsten Stehlik, Jason Lam, Lazar Dimitrov, Thomas Heimerl, Isabelle Schöck, Jannik Harberding, Anita Dornes, Nikola Heymons, Gert Bange, Maya Schuldiner, Einat Zalckvar, Michael Bölker, Randy Schekman, Johannes Freitag

Peroxisomes are organelles with crucial functions in oxidative metabolism. To correctly target to peroxisomes, proteins require specialized targeting signals. A mystery in the field is the sorting of proteins that carry a targeting signal for peroxisomes and as well as for other organelles, such as mitochondria or the endoplasmic reticulum (ER). Exploring several of these proteins in fungal model systems, we observed that they can act as tethers bridging organelles together to create contact sites. We show that in Saccharomyces cerevisiae this mode of tethering involves the peroxisome import machinery, the ER–mitochondria encounter structure (ERMES) at mitochondria and the guided entry of tail-anchored proteins (GET) pathway at the ER. Our findings introduce a previously unexplored concept of how dual affinity proteins can regulate organelle attachment and communication.