Mitochondria are key regulators of many important cellular processes, and their dysfunction has been implicated in a large number of human disorders and aging. Importantly, mitochondrial function is closely linked to their ultrastructure, which possesses an intricate membrane architecture defining specific submitochondrial compartments. In particular, the mitochondrial inner membrane is highly folded into membrane invaginations that are essential for oxidative phosphorylation. Furthermore, mitochondrial membranes are highly dynamic and undergo constant membrane remodeling during mitochondrial fusion and fission. It has remained enigmatic how these membrane curvatures are generated and maintained, and the specific factors involved in these processes remain largely unknown. We aim to elucidate the molecular principles by which mitochondrial proteins interact with lipid membranes and remodel mitochondrial membrane ultrastructure and dynamics.
In mammals, mitochondria synthesize 13 proteins, all of which are essential components of the oxidative phosphorylation (OXPHOS) complexes. These predominantly hydrophobic proteins are synthesized by specialized mitochondrial ribosomes (mitoribosomes) located in the matrix and associated with the inner mitochondrial membrane. This association facilitates the co-translational insertion of newly synthesized proteins. The mammalian mitoribosome has a sedimentation coefficient of 55S and consists of two subunits: the large subunit (mt-LSU, 39S) and the small subunit (mt-SSU, 28S). These subunits contain 16S and 12S mitoribosome RNAs (mt-rRNA), respectively, along with over 80 mitoribosome proteins (MRPs). The biogenesis of each subunit follows an independent pathway that involves the import, processing, and assembly of nuclear-encoded MRPs, as well as post-transcriptional processing of the mt-rRNAs. The assembly of the mitoribosome is facilitated by various assembly factors temporarily associated with the nascent ribosome, ensuring its accurate and efficient construction. These assembly factors encompass rRNA processing and modifying enzymes, RNA helicases, chaperones, and GTPases. Our research focuses on elucidating the cellular roles of GTPases involved in mitoribosome assembly.