bims-tricox 2023-05-21 papers

Issue of 2023‒05‒21
four papers selected by
Yash Verma
University of Zurich

Cell. 2023 May 11. pii: S0092-8674(23)00464-6. [Epub ahead of print]186(10): 2282-2282.e1

SnapShot: Eukaryotic ribosome biogenesis I.

Ed Hurt, Jingdong Cheng, Jochen Baβler, Janet Iwasa, Roland Beckmann.

Ribosome production is vital for every cell, and failure causes human diseases. It is driven by ∼200 assembly factors functioning along an ordered pathway from the nucleolus to the cytoplasm. Structural snapshots of biogenesis intermediates from the earliest 90S pre-ribosomes to mature 40S subunits unravel the mechanisms of small ribosome synthesis. To view this SnapShot, open or download the PDF.

DOI: https://doi.org/10.1016/j.cell.2023.04.030

IUBMB Life. 2023 May 13.

The role of the proteasome in mitochondrial protein quality control.

Saskia Rödl, Johannes M Herrmann.

The abundance of each cellular protein is dynamically adjusted to the prevailing metabolic and stress conditions by modulation of their synthesis and degradation rates. The proteasome represents the major machinery for the degradation of proteins in eukaryotic cells. How the ubiquitin-proteasome system (UPS) controls protein levels and removes superfluous and damaged proteins from the cytosol and the nucleus is well characterized. However, recent studies showed that the proteasome also plays a crucial role in mitochondrial protein quality control. This mitochondria-associated degradation (MAD) thereby acts on two layers: first, the proteasome removes mature, functionally compromised or mis-localized proteins from the mitochondrial surface; and second, the proteasome cleanses the mitochondrial import pore of import intermediates of nascent proteins that are stalled during translocation. In this review, we provide an overview about the components and their specific functions that facilitate proteasomal degradation of mitochondrial proteins in the yeast Saccharomyces cerevisiae. Thereby we explain how the proteasome, in conjunction with a set of intramitochondrial proteases, maintains mitochondrial protein homeostasis and dynamically adapts the levels of mitochondrial proteins to specific conditions.

Keywords: mitochondria; mitochondria-associated degradation; proteasome; protein degradation; protein import; ubiquitin

DOI: https://doi.org/10.1002/iub.2734

Nucleic Acids Res. 2023 May 19. pii: gkad422. [Epub ahead of print]

Miniature RNAs are embedded in an exceptionally protein-rich mitoribosome via an elaborate assembly pathway.

Matus Valach, Corinna Benz, Lisbeth C Aguilar, Ondřej Gahura, Drahomíra Faktorová, Alena Zíková, Marlene Oeffinger, Gertraud Burger, Michael W Gray, Julius Lukeš.

The mitochondrial ribosome (mitoribosome) has diverged drastically from its evolutionary progenitor, the bacterial ribosome. Structural and compositional diversity is particularly striking in the phylum Euglenozoa, with an extraordinary protein gain in the mitoribosome of kinetoplastid protists. Here we report an even more complex mitoribosome in diplonemids, the sister-group of kinetoplastids. Affinity pulldown of mitoribosomal complexes from Diplonema papillatum, the diplonemid type species, demonstrates that they have a mass of > 5 MDa, contain as many as 130 integral proteins, and exhibit a protein-to-RNA ratio of 11:1. This unusual composition reflects unprecedented structural reduction of ribosomal RNAs, increased size of canonical mitoribosomal proteins, and accretion of three dozen lineage-specific components. In addition, we identified >50 candidate assembly factors, around half of which contribute to early mitoribosome maturation steps. Because little is known about early assembly stages even in model organisms, our investigation of the diplonemid mitoribosome illuminates this process. Together, our results provide a foundation for understanding how runaway evolutionary divergence shapes both biogenesis and function of a complex molecular machine.

DOI: https://doi.org/10.1093/nar/gkad422

Genetics. 2023 May 15. pii: iyad087. [Epub ahead of print]

y-mtPTM: Yeast Mitochondrial Post-Translational Modification Database.

Bronislava Brejová, Veronika Vozáriková, Ivan Agarský, Hana Derková, Matej Fedor, Dominika Harmanová, Lukáš Kiss, Andrej Korman, Martin Pašen, Filip Brázdovič, Tomáš Vinař, Jozef Nosek, Ľubomír Tomáška.

One powerful strategy of how to increase the complexity of cellular proteomes is through post-translational modifications (PTMs) of proteins. Currently there are approximately 400 types of PTMs, the different combinations of which yield a large variety of protein isoforms with distinct biochemical properties. Although mitochondrial proteins undergoing PTMs were identified nearly six decades ago, studies on the roles and extent of PTMs on mitochondrial functions lagged behind the other cellular compartments. The application of mass spectrometry for the characterization of the mitochondrial proteome as well as for the detection of various PTMs resulted in the identification of thousands of amino acid positions that can be modified by different chemical groups. However, the data on mitochondrial PTMs are scattered in several datasets, and the available databases do not contain a complete list of modified residues. To integrate information on PTMs of the mitochondrial proteome of the yeast Saccharomyces cerevisiae, we built the y-mtPTM (Yeast Mitochondrial Post-Translational Modification) Database (http://compbio.fmph.uniba.sk/y-mtptm/). It lists nearly 20,000 positions on mitochondrial proteins affected by approximately twenty various PTMs, with phosphorylated, succinylated, acetylated and ubiquitylated sites being the most abundant. A simple search of a protein of interest reveals the modified amino acid residues, their position within the primary sequence as well as on its 3D structure and links to the source reference(s). The database will serve yeast mitochondrial researchers as a comprehensive platform to investigate the functional significance of the PTMs of mitochondrial proteins.

Keywords: acetylation; database; mitochondria; phosphorylation; post-translational modifications; succinylation; yeast

DOI: https://doi.org/10.1093/genetics/iyad087