bims-tricox 2022-11-27 papers

Int J Mol Sci. 2022 Nov 10. pii: 13880. [Epub ahead of print]23(22):

Mitochondrial Respiratory Chain Supercomplexes: From Structure to Function.

Mitochondrial oxidative phospho rylation, the center of cellular metabolism, is pivotal for the energy production in eukaryotes. Mitochondrial oxidative phosphorylation relies on the mitochondrial respiratory chain, which consists of four main enzyme complexes and two mobile electron carriers. Mitochondrial enzyme complexes also assemble into respiratory chain supercomplexes (SCs) through specific interactions. The SCs not only have respiratory functions but also improve the efficiency of electron transfer and reduce the production of reactive oxygen species (ROS). Impaired assembly of SCs is closely related to various diseases, especially neurodegenerative diseases. Therefore, SCs play important roles in improving the efficiency of the mitochondrial respiratory chain, as well as maintaining the homeostasis of cellular metabolism. Here, we review the structure, assembly, and functions of SCs, as well as the relationship between mitochondrial SCs and diseases.

Keywords: assembly; cytochrome c; mitochondria; respiratory chain; supercomplexes

DOI: https://doi.org/10.3390/ijms232213880

Front Microbiol. 2022 ;13 999176

Single-molecule dynamics suggest that ribosomes assemble at sites of translation in Bacillus subtilis.

Joshua Stoll, Victor Zegarra, Gert Bange, Peter L Graumann.

Eukaryotic cells transcribe ribosomal RNA and largely assemble ribosomes in a structure called the nucleolus, where chromosomal regions containing rRNA operons are clustered. In bacteria, many rRNA operons cluster close to the origin regions that are positioned on the outer borders of nucleoids, close to polar areas, where translating 70S ribosomes are located. Because outer regions of the nucleoids contain the highest accumulation of RNA polymerase, it has been hypothesized that bacteria contain "nucleolus-like" structures. However, ribosome subunits freely diffuse through the entire cells, and could thus be assembled and matured throughout the non-compartmentalized cell. By tracking single molecules of two GTPases that play an essential role in ribosomal folding and processing in Bacillus subtilis, we show that this process takes place at sites of translation, i.e., predominantly at the cell poles. Induction of the stringent response led to a change in the population of GTPases assumed to be active in maturation, but did not abolish nucleoid occlusion of ribosomes or of GTPases. Our findings strongly support the idea of the conceptualization of nucleolus-like structures in bacteria, i.e., rRNA synthesis, ribosomal protein synthesis and subunit assembly occurring in close proximity at the cell poles, facilitating the efficiency of ribosome maturation even under conditions of transient nutrient deprivation.

Keywords: Bacillus subtilis; GTPase; bacterial cell biology; nucleoid occlusion; ribosome assembly; single molecule tracking; translation

DOI: https://doi.org/10.3389/fmicb.2022.999176

Cell Rep. 2022 Nov 22. pii: S2211-1247(22)01558-3. [Epub ahead of print]41(8): 111684

Cms1 coordinates stepwise local 90S pre-ribosome assembly with timely snR83 release.

Benjamin Lau, Olga Beine-Golovchuk, Markus Kornprobst, Jingdong Cheng, Dieter Kressler, Beáta Jády, Tamás Kiss, Roland Beckmann, Ed Hurt.

Ribosome synthesis begins in the nucleolus with 90S pre-ribosome construction, but little is known about how the many different snoRNAs that modify the pre-rRNA are timely guided to their target sites. Here, we report a role for Cms1 in such a process. Initially, we discovered CMS1 as a null suppressor of a nop14 mutant impaired in Rrp12-Enp1 factor recruitment to the 90S. Further investigations detected Cms1 at the 18S rRNA 3' major domain of an early 90S that carried H/ACA snR83, which is known to guide pseudouridylation at two target sites within the same subdomain. Cms1 co-precipitates with many 90S factors, but Rrp12-Enp1 encircling the 3' major domain in the mature 90S is decreased. We suggest that Cms1 associates with the 3' major domain during early 90S biogenesis to restrict premature Rrp12-Enp1 binding but allows snR83 to timely perform its modification role before the next 90S assembly steps coupled with Cms1 release take place.

Keywords: 90S pre-ribosome; CP: Molecular biology; H/ACA; RNA modification; pre-rRNA; pseudouridylation; ribosome assembly; snoRNA; suppressor; yeast

DOI: https://doi.org/10.1016/j.celrep.2022.111684

Mol Cell. 2022 Nov 16. pii: S1097-2765(22)01061-9. [Epub ahead of print]

Chromatin localization of nucleophosmin organizes ribosome biogenesis.

Ilaria Ugolini, Silvija Bilokapic, Mylene Ferrolino, Josiah Teague, Yinxia Yan, Xuelin Zhou, Ashish Deshmukh, Michael White, Richard W Kriwacki, Mario Halic.

Ribosome biogenesis takes place in the nucleolus, a nuclear membrane-less organelle. Although well studied, it remains unknown how nascent ribosomal subunits separate from the central chromatin compartment and move to the outer granular component, where maturation occurs. We find that the Schizosaccharomyces pombe nucleophosmin-like protein Fkbp39 localizes to rDNA sites encoding the 60S subunit rRNA, and this localization contributes to its specific association with nascent 60S subunits. Fkbp39 dissociates from chromatin to bind nascent 60S subunits, causing the latter to partition away from chromatin and from nascent 40S subunits through liquid-liquid phase separation. In vivo, Fkbp39 binding directs the translocation of nascent 60S subunits toward the nucleophosmin-rich granular component. This process increases the efficiency of 60S subunit assembly, facilitating the incorporation of 60S RNA domain III. Thus, chromatin localization determines the specificity of nucleophosmin in sorting nascent ribosomal subunits and coordinates their movement into specialized assembly compartments within the nucleolus.

Keywords: NPM1; chromatin; cryo-EM; fkbp; liquid-liquid phase separation; nascent 60S; nucleophosmin; ribosome biogenesis

DOI: https://doi.org/10.1016/j.molcel.2022.10.033

Biochim Biophys Acta Bioenerg. 2022 Nov 17. pii: S0005-2728(22)00403-0. [Epub ahead of print]1864(2): 148933

Structures of the intermediates in the catalytic cycle of mitochondrial cytochrome c oxidase.

Mårten Wikström, Robert B Gennis, Peter R Rich.

Keywords: Cell respiration; Heme‑copper oxidases; Oxygen reduction; Respiratory chain

DOI: https://doi.org/10.1016/j.bbabio.2022.148933

Int J Mol Sci. 2022 Nov 08. pii: 13694. [Epub ahead of print]23(22):

Understanding the Role of Yeast Yme1 in Mitochondrial Function Using Biochemical and Proteomics Analyses.

Kwan Ting Kan, Michael G Nelson, Chris M Grant, Simon J Hubbard, Hui Lu.

Mitochondrial i-AAA proteinase Yme1 is a multifunctional protein that plays important roles in maintaining mitochondrial protein homeostasis and regulating biogenesis and function of mitochondrial proteins. However, due to the complex interplay of mitochondria and the multifunctional nature of Yme1, how Yme1 affects mitochondrial function and protein homeostasis is still poorly understood. In this study, we investigated how YME1 deletion affects yeast Saccharomyces cerevisiae growth, chronological life span, mitochondrial protein homeostasis and function, with a focus on the mitochondrial oxidative phosphorylation (OXPHOS) complexes. Our results show that whilst the YME1 deleted cells grow poorly under respiratory conditions, they grow similar to wild-type yeast under fermentative conditions. However, the chronological life span is impaired, indicating that Yme1 plays a key role in longevity. Using highly enriched mitochondrial extract and proteomic analysis, we show that the abundances of many mitochondrial proteins are altered by YME1 deletion. Several components of the respiratory chain complexes II, III, IV and V were significantly decreased, suggesting that Yme1 plays an important role in maintaining the level and function of complexes II-V. This result was confirmed using blue native-PAGE and in-solution-based enzyme activity assays. Taken together, this study shows that Yme1 plays an important role in the chronological life span and mitochondrial protein homeostasis and has deciphered its function in maintaining the activity of mitochondrial OXPHOS complexes.

Keywords: AAA proteinase; OXPHOS complex; mitochondrial function; mitochondrial proteomics

DOI: https://doi.org/10.3390/ijms232213694