Prof.Alexey Amunts
Science for Life Laboratory, Sweden

What can we learn from structural studies of mitochondrial complexes

The mitoribosome translates specific mitochondrial mRNAs and regulates energy production
that is a signature of all eukaryotic life forms. We present cryo-EM analyses of its assembly
intermediates, mRNA binding process, and nascent polypeptide delivery to the membrane. To
study the assembly mechanism, we determined a series of the small mitoribosomal subunit
intermediates in complex with auxiliary factors that explain how action of step-specific factors
establishes the catalytic mitoribosome. A delivery of mRNA is then performed by a helical
repeat factor LRPPRC that forms a stable complex with a small binding partner SLIRP. In
mammals, LRPPRC stabilises mRNAs co-transcriptionally, thus it links the entire gene
expression system. Through the translation cycle, a nascent polypeptide is delivered to the
mitochondrial inner membrane, and we report the mitoribosome structure bound to the
insertase OXA1, which elucidates the basis for protein synthesis coupling to membrane
delivery. Together with experimental identification of functionally non-protein cofactors and
specific rRNA and protein modifications, the data illuminate principal components responsible
for the translation of genetic material in mitochondria.