bims-cytox1 2021-10-03 papers

Issue of 2021–10–03
four papers selected by
Gavin McStay, Staffordshire University

Nat Commun. 2021 Sep 29. 12(1): 5715

Mapping protein interactions in the active TOM-TIM23 supercomplex.

Ridhima Gomkale, Andreas Linden, Piotr Neumann, Alexander Benjamin Schendzielorz, Stefan Stoldt, Olexandr Dybkov, Markus Kilisch, Christian Schulz, Luis Daniel Cruz-Zaragoza, Blanche Schwappach, Ralf Ficner, Stefan Jakobs, Henning Urlaub, Peter Rehling.

Nuclear-encoded mitochondrial proteins destined for the matrix have to be transported across two membranes. The TOM and TIM23 complexes facilitate the transport of precursor proteins with N-terminal targeting signals into the matrix. During transport, precursors are recognized by the TIM23 complex in the inner membrane for handover from the TOM complex. However, we have little knowledge on the organization of the TOM-TIM23 transition zone and on how precursor transfer between the translocases occurs. Here, we have designed a precursor protein that is stalled during matrix transport in a TOM-TIM23-spanning manner and enables purification of the translocation intermediate. Combining chemical cross-linking with mass spectrometric analyses and structural modeling allows us to map the molecular environment of the intermembrane space interface of TOM and TIM23 as well as the import motor interactions with amino acid resolution. Our analyses provide a framework for understanding presequence handover and translocation during matrix protein transport.

DOI: https://doi.org/10.1038/s41467-021-26016-1

Biochemistry (Mosc). 2021 Sep;86(9): 1151-1161

Yeast Translational Activator Mss51p and Human ZMYND17 - Two Proteins with a Common Origin, but Different Functions.

Maria V Baleva, Uliyana E Piunova, Ivan V Chicherin, Darya G Krasavina, Sergey A Levitskii, Piotr A Kamenski.

Despite its similarity to protein biosynthesis in bacteria, translation in the mitochondria of modern eukaryotes has several unique features, such as the necessity for coordination of translation of mitochondrial mRNAs encoding proteins of the electron transport chain complexes with translation of other protein components of these complexes in the cytosol. In the mitochondria of baker's yeast Saccharomyces cerevisiae, this coordination is carried out by a system of translational activators that predominantly interact with the 5'-untranslated regions of mitochondrial mRNAs. No such system has been found in human mitochondria, except a single identified translational activator, TACO1. Here, we studied the role of the ZMYND17 gene, an ortholog of the yeast gene for the translational activator Mss51p, on the mitochondrial translation in human cells. Deletion of the ZMYND17 gene did not affect translation in the mitochondria, but led to the decrease in the cytochrome c oxidase activity and increase in the amount of free F1 subunit of ATP synthase. We also investigated the evolutionary history of Mss51p and ZMYND17 and suggested a possible mechanism for the divergence of functions of these orthologous proteins.

Keywords: mitochondria; translation; translation regulation; translational activators

DOI: https://doi.org/10.1134/S0006297921090108

Cells. 2021 Aug 25. pii: 2198. [Epub ahead of print]10(9):

Down the Iron Path: Mitochondrial Iron Homeostasis and Beyond.

Jonathan V Dietz, Jennifer L Fox, Oleh Khalimonchuk.

Cellular iron homeostasis and mitochondrial iron homeostasis are interdependent. Mitochondria must import iron to form iron-sulfur clusters and heme, and to incorporate these cofactors along with iron ions into mitochondrial proteins that support essential functions, including cellular respiration. In turn, mitochondria supply the cell with heme and enable the biogenesis of cytosolic and nuclear proteins containing iron-sulfur clusters. Impairment in cellular or mitochondrial iron homeostasis is deleterious and can result in numerous human diseases. Due to its reactivity, iron is stored and trafficked through the body, intracellularly, and within mitochondria via carefully orchestrated processes. Here, we focus on describing the processes of and components involved in mitochondrial iron trafficking and storage, as well as mitochondrial iron-sulfur cluster biogenesis and heme biosynthesis. Recent findings and the most pressing topics for future research are highlighted.

Keywords: heme biosynthesis; iron homeostasis; iron trafficking; mitochondrial iron–sulfur clusters

DOI: https://doi.org/10.3390/cells10092198

Genes (Basel). 2021 Aug 24. pii: 1303. [Epub ahead of print]12(9):

Yeast as a Tool to Understand the Significance of Human Disease-Associated Gene Variants.

Tiziana Cervelli, Alvaro Galli.

At present, the great challenge in human genetics is to provide significance to the growing amount of human disease-associated gene variants identified by next generation DNA sequencing technologies. Increasing evidences suggest that model organisms are of pivotal importance to addressing this issue. Due to its genetic tractability, the yeast Saccharomyces cerevisiae represents a valuable model organism for understanding human genetic variability. In the present review, we show how S. cerevisiae has been used to study variants of genes involved in different diseases and in different pathways, highlighting the versatility of this model organism.

Keywords: Mendelian disease; Saccharomyces cerevisiae; cancer; functional assays; human gene variants; yeast

DOI: https://doi.org/10.3390/genes12091303