Ups delivery to the intermembrane space of mitochondria: a novel affinity-driven protein import pathway

Abstract

Mitochondria are comprised of two aqueous subcompartments: the matrix and the intermembrane space (IMS). Following their synthesis on cytosolic ribosomes, proteins destined to the matrix are threaded by N‐terminal matrix‐targeting sequences through TOM and TIM translocases in the outer and the inner membrane of the organelle. Proteins of the IMS often lack such presequences, and the principles mediating their uptake into mitochondria are diverse and poorly understood. In this issue, [Potting et al (2010)][1] and [Tamura et al (2010)][2] show that Ups proteins, a group of soluble IMS proteins critical for lipid homeostasis, adsorb to the IMS factor Mdm35 after their translocation across the outer membrane. Mdm35 thereby apparently functions as an intramitochondrial acceptor protein. The existence of affinity‐driven import routes has been proposed before, but Mdm35 represents the first intramitochondrial acceptor protein that is identified. [1]: #ref-9 [2]: #ref-12