bims-cytox1 2022-07-17 papers

on Cytochrome oxidase subunit 1

Issue of 2022–07–17
two papers selected by
Gavin McStay, Liverpool John Moores University

Cryo-EM structure of a monomeric yeast S. cerevisiae complex IV isolated with maltosides: Implications in supercomplex formation.
The nuclear encoded Cox7c mRNA co-transport with mitochondria along axons via coding-region dependent mechanism.

Biochim Biophys Acta Bioenerg. 2022 Jul 12. pii: S0005-2728(22)00060-3. [Epub ahead of print] 148591

Cryo-EM structure of a monomeric yeast S. cerevisiae complex IV isolated with maltosides: Implications in supercomplex formation.

Gabriel Ing, Andrew M Hartley, Nikos Pinotsis, Amandine Maréchal.

  In mitochondria, complex IV (CIV) can be found as a monomer, a dimer or in association with other respiratory complexes. The atomic structure of the yeast S. cerevisiae CIV in a supercomplex (SC) with complex III (CIII) pointed to a region of significant conformational changes compared to the homologous mammalian CIV structures. These changes involved the matrix side domain of Cox5A at the CIII-CIV interface, and it was suggested that it could be required for SC formation. To investigate this, we solved the structure of the isolated monomeric CIV from S. cerevisiae stabilised in amphipol A8-35 at 3.9 Å using cryo-electron microscopy. Only a minor change in flexibility was seen in this Cox5A region, ruling out large CIV conformational shift for interaction with CIII and confirming the different fold of the yeast Cox5A subunit compared to mammalian homologues. Other differences in structure were the absence of two canonical subunits, Cox12 and Cox13, as well as Cox26, which is unique to the yeast CIV. Their absence is most likely due to the protein purification protocol used to isolate CIV from the III-IV SC.

Keywords:  Amphipols; Bioenergetics; Cytochrome c oxidase; Electron transport chain; Mitochondria; Supercomplexes

DOI:  https://doi.org/10.1016/j.bbabio.2022.148591
J Cell Sci. 2022 Jul 14. pii: jcs.259436. [Epub ahead of print]

The nuclear encoded Cox7c mRNA co-transport with mitochondria along axons via coding-region dependent mechanism.

Bar Cohen, Topaz Altman, Adi Golani-Armon, Anca F Savulescu, Amjd Ibraheem, Musa M Mhlanga, Eran Perlson, Yoav S Arava.

  Nuclear encoded mitochondrial protein mRNAs have been found to be localized and locally translated within neuronal processes. However, the transport mechanism of those mRNAs to distal locations is not fully understood. Here, we describe axonal co-transport of Cox7c with mitochondria. Fractionation analysis and smFISH assay revealed that endogenous mRNA encoding Cox7c is preferentially associated with mitochondria from a neuronal cell line and within primary motor neuron axons, while other mRNAs, which do not encode mitochondrial protein are much less associated. Live cell imaging of MS2-tagged Cox7c mRNA further confirmed the preferential colocalization and co-transport of Cox7c mRNA with mitochondria in motor neuron axons. Intriguingly, the coding region, rather than the 3' UTR, was the key domain for the cotransport. Our results reveal that Cox7c mRNA can be transported with mitochondria along significant distances and its coding region is a major recognition feature. This is consistent with the idea that mitochondria can play a vital role in spatial regulation of the axonal transcriptome at distant neuronal sites.

Keywords:  Axonal transport; Cox7c; Mitochondria; mRNA localization; mRNA transport

DOI:  https://doi.org/10.1242/jcs.259436