Biology subjects

Rampelt, H.

Publications and source records attributed to Rampelt, H..

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↗

bioRxiv2024

RNA promotes mitochondrial import of F1-ATP synthase subunit alpha (ATP5A1)

Most mitochondrial proteins are encoded by the nuclear genome, translated as precursor proteins in the cytosol and matured during directed import into the mitochondria 1. For many mitochondrial proteins this process is carefully regulated to meet demand and to avoid mitochondrial stress 2,3,4. Recently, mitochondrial F1-ATP synthase subunits have been found to interact with RNA across various eukaryotes. This includes genome wide RNA-interactome studies from yeast 5-7, fruit flies 8,9, plants 10-12, mice 13-17 and humans 18-24. To shed light on this unexpected observation, we determined the interacting cellular RNAs of ATP5A1 and the subcellular sites of interaction. Using RNA binding-deficient mutants of ATP5A1 and functional assays, we show that specific cytosolic RNAs bind ATP5A1 precursor proteins at the outer surface of mitochondria and promote their mitochondrial import both in vitro and in cellulo. These findings add an unexpected twist to understanding mitochondrial protein import and expand the growing list of riboregulated cellular processes.

cell biology↗

bioRxiv2024

Coordination of cytochrome bc1 complex assembly at MICOS

The boundary and cristae domains of the mitochondrial inner membrane are connected by crista junctions. Most cristae membrane proteins are nuclear-encoded and inserted by the mitochondrial protein import machinery into the inner boundary membrane. Thus, they must overcome the diffusion barrier imposed by crista junctions to reach their final location. Here, we show that respiratory chain complexes and assembly intermediates are physically connected to the mitochondrial contact site and cristae organizing system (MICOS) that is essential for formation and stability of crista junctions. We identify the inner membrane protein Mar26 (Fmp10) as determinant in the biogenesis of the cytochrome bc1 complex (complex III). Mar26 couples a Rieske Fe/S protein-containing assembly intermediate to MICOS. Our data indicate that Mar26 maintains an assembly-competent Rip1 pool at crista junctions where complex III maturation likely occurs. MICOS facilitates efficient Rip1 assembly by recruitment of complex III assembly intermediates to crista junctions. We propose that MICOS, via interaction with assembly factors such as Mar26, directly contributes to the spatial and temporal coordination of respiratory chain biogenesis.

biochemistry↗