bims-tricox 2024-04-21 papers

Issue of 2024‒04‒21
four papers selected by
Yash Verma, University of Zurich

Biochem Soc Trans. 2024 Apr 17. pii: BST20231236. [Epub ahead of print]

New insights into the structure and dynamics of the TOM complex in mitochondria.

Stephan Nussberger, Robin Ghosh, Shuo Wang.

To date, there is no general physical model of the mechanism by which unfolded polypeptide chains with different properties are imported into the mitochondria. At the molecular level, it is still unclear how transit polypeptides approach, are captured by the protein translocation machinery in the outer mitochondrial membrane, and how they subsequently cross the entropic barrier of a protein translocation pore to enter the intermembrane space. This deficiency has been due to the lack of detailed structural and dynamic information about the membrane pores. In this review, we focus on the recently determined sub-nanometer cryo-EM structures and our current knowledge of the dynamics of the mitochondrial two-pore outer membrane protein translocation machinery (TOM core complex), which provide a starting point for addressing the above questions. Of particular interest are recent discoveries showing that the TOM core complex can act as a mechanosensor, where the pores close as a result of interaction with membrane-proximal structures. We highlight unusual and new correlations between the structural elements of the TOM complexes and their dynamic behavior in the membrane environment.

Keywords: Tom complex; electron cryo-microscopy; mechanosensitivity; mitochondria; protein translocation; single-molecule microscopy

DOI: https://doi.org/10.1042/BST20231236

NAR Genom Bioinform. 2024 Jun;6(2): lqae036

A data-driven estimation of the ribosome drop-off rate in S. cerevisiae reveals a correlation with the genes length.

Sherine Awad, Angelo Valleriani, Davide Chiarugi.

Ribosomes are the molecular machinery that catalyse all the fundamental steps involved in the translation of mRNAs into proteins. Given the complexity of this process, the efficiency of protein synthesis depends on a large number of factors among which ribosome drop-off (i.e. the premature detachment of the ribosome from the mRNA template) plays an important role. However, an in vitro quantification of the extent to which ribosome drop-off occurs is not trivial due to difficulties in obtaining the needed experimental evidence. In this work we focus on the study of ribosome drop-off in Saccharomyces cerevisiae by using 'Ribofilio', a novel software tool that relies on a high sensitive strategy to estimate the ribosome drop-off rate from ribosome profiling data. Our results show that ribosome drop-off events occur at a significant rate also when S. cerevisiae is cultured in standard conditions. In this context, we also identified a correlation between the ribosome drop-off rate and the genes length: the longer the gene, the lower the drop-off rate.

DOI: https://doi.org/10.1093/nargab/lqae036

J Cell Biol. 2024 May 06. pii: e202403190. [Epub ahead of print]223(5):

OMA1 clears traffic jam in TOM tunnel in mammals.

Shiori Sekine, Yusuke Sekine.

Using an engineered mitochondrial clogger, Krakowczyk et al. (https://doi.org/10.1083/jcb.202306051) identified the OMA1 protease as a critical component that eliminates import failure at the TOM translocase in mammalian cells, providing a novel quality control mechanism that is distinct from those described in yeast.

DOI: https://doi.org/10.1083/jcb.202403190

Biochim Biophys Acta Mol Cell Res. 2024 Apr 17. pii: S0167-4889(24)00076-4. [Epub ahead of print] 119733

Mitochondria function in cytoplasmic FeS protein biogenesis.

Andrew Dancis, Ashutosh K Pandey, Debkumar Pain.

Iron‑sulfur (FeS) clusters are cofactors of numerous proteins involved in various essential functions including cellular respiration, protein translation, DNA synthesis and repair, ribosome maturation, anti-viral responses, and isopropylmalate isomerase activity. Novel FeS cluster proteins are still being discovered due to the widespread use of cryogenic electron microscopy (cryo-EM) and elegant genetic screens targeted at protein discovery. A complex sequence of biochemical reactions mediated by a conserved machinery controls biosynthesis of FeS clusters. In eukaryotes, a remarkable epistasis has been observed: the mitochondrial machinery, termed ISC (Iron-Sulfur Cluster), lies upstream of the cytoplasmic machinery, termed CIA (Cytoplasmic Iron‑sulfur protein Assembly). The basis for this arrangement is the production of a hitherto uncharacterized intermediate, termed X-S or (FeS)int, produced in mitochondria by the ISC machinery, exported by the mitochondrial ABC transporter Atm1 (ABC7 in humans), and then utilized by the CIA machinery for the cytoplasmic/nuclear FeS cluster assembly. Genetic and biochemical findings supporting this sequence of events are herein presented. New structural views of the Atm1 transport phases are reviewed. The key compartmental roles of glutathione in cellular FeS cluster biogenesis are highlighted. Finally, data are presented showing that every one of the ten core components of the mitochondrial ISC machinery and Atm1, when mutated or depleted, displays similar phenotypes: mitochondrial and cytoplasmic FeS clusters are both rendered deficient, consistent with the epistasis noted above.

Keywords: (FeS)(int); Atm1; Cytoplasm; FeS cluster trafficking; FeS proteins; Glutaredoxin; Glutathione; Mitochondria; X-S

DOI: https://doi.org/10.1016/j.bbamcr.2024.119733