Biology subjects

Steiert, C.

Publications and source records attributed to Steiert, C..

3 recordsLinked to original sources

bioRxiv2026

Super-resolution complexome of human mitochondria elucidates translocase, morphology and OXPHOS networks

Mitochondria function as cellular powerhouses and central hubs in metabolism, redox and stress reactions, signaling and apoptosis1-5. Defects of mitochondria lead to numerous human diseases1,6-8. The integration of mitochondrial proteins into complexes and networks is crucial for their function. Whereas the composition of the human mitochondrial proteome has been studied8,9, only limited information is available on the organization of the proteome into protein complexes and assemblies. Here we present a systematic mapping of the human mitochondrial complexome from HEK293T cells at super-resolution, resolving more than 7,000 abundance profile peaks of mitochondrial proteins. Proteins functioning in signaling, cell stress, protein biogenesis, turnover and membrane dynamics display particularly high complexities. High resolution and precise quantification enable discrimination between canonical constituents and non-stoichiometric regulatory interactors of the ATP synthase, major metabolite channels and import translocases. The complexome reveals membrane-spanning networks of protein insertase and morphology machinery, and co-assembly of protein import and export components at the major respiratory supercomplex, unraveling a multifunctional organization of mitochondrial machineries. This complexome represents a fully interactive resource for the systematic analysis of human mitochondrial machineries and interaction networks.

biochemistry↗

bioRxiv2026

A dynamic displacement mechanism drives protein import into mitochondria

Most mitochondrial proteins are produced in the cytosol and imported through the translocase of the outer mitochondrial membrane (TOM) to reach their final destination. Although this protein entry gate has been structurally characterized, it remains unclear how precursor proteins are handed off from the cytosolic receptor domains to the translocation pore. Here we show that the cytosolic domain of Tom22--traditionally viewed as the central TOM receptor--acts not as a structured scaffold but as a largely disordered, flexible segment that plays an active role in precursor transfer. Atomic-level structural techniques and in vivo experiments identified a conserved short linear motif that forms a transient !-helical element within this disordered domain. By binding to the canonical precursor protein binding sites of the receptors Tom20 and Tom70, this critical -helical segment acts as a precursor protein displacement element (PPDE). This competitive interaction facilitates the release of preproteins directly above the import pore, and thereby drives translocation across the outer mitochondrial membrane. These findings reveal that flexibility, rather than rigid structure, underlies the central transfer step of mitochondrial outermembrane protein translocation. Our results point to a versatile mechanism for ligand displacement in chaperone, receptor, and transport systems that must balance selective binding with efficient release.

cell biology↗

bioRxiv2023

Role of the small protein Mco6 in the mitochondrial sorting and assembly machinery

The majority of mitochondrial precursor proteins are imported through the Tom40 {beta}-barrel channel of the translocase of the outer membrane (TOM). The sorting and assembly machinery (SAM) is essential for {beta}-barrel membrane protein insertion into the outer membrane and thus required for the assembly of the TOM complex. Here we demonstrate that the a-helical outer membrane protein Mco6 forms a complex with the mitochondrial distribution and morphology protein Mdm10 as part of the SAM machinery. Moreover, Mco6 also interacts with the subunit Mim1 of the mitochondrial import complex (MIM), which is itself required for the biogenesis of a-helical outer membrane proteins. MCO6 and MDM10 display a negative genetic interaction and a MCO6-MDM10 yeast double mutant contains reduced levels of TOM complex. Cells lacking Mco6 affect the levels of Mdm10 and MIM-subunits associated with assembly defects of the TOM complex. Thus, this work reveals a role of the SAMMco6 complex for the biogenesis of the mitochondrial outer membrane.

cell biology↗