Biology subjects

Topf, U.

Publications and source records attributed to Topf, U..

3 recordsLinked to original sources

bioRxiv2026

Rpl40/eL40 ribosomal protein paralogs couple cytosolic translation to mitochondrial proteome and lipid homeostasis

Ribosomal protein paralogs are increasingly implicated in the regulation of cellular metabolism and mitochondrial function. However, the mechanisms linking paralog composition of ribosomes to mitochondrial physiology remain largely unclear. Here, we investigate the two Rpl40 paralogs in the budding yeast Saccharomyces cerevisiae and find that deletion of either paralog induces compensatory upregulation of the remaining gene and causes mild mitochondrial stress. Despite this shared phenotype, the mutants display distinct mitochondrial adaptations. Loss of Rpl40a is accompanied by increased abundance of mitochondrial proteins, including MICOS components, whereas loss of Rpl40b leads to reduced levels of mitochondrial inner membrane proteins, including the translocase Tim22 and carrier proteins, together with increased sensitivity to membrane stress. Notably, the two mutants show opposing changes in triglyceride abundance, pointing to paralog-specific control of lipid metabolic remodeling during mitochondrial stress. These findings suggest that Rpl40 paralogs differentially modulate cellular adaptation to mitochondrial stress, linking ribosome composition to mitochondrial proteostasis and lipid homeostasis.

biochemistry↗

bioRxiv2024

Identification of a non-canonical function of prefoldin subunit 5 in proteasome assembly

The prefoldin complex is a heterohexameric, evolutionarily conserved co-chaperone that assists in the folding of polypeptides downstream of the protein translation machinery. Loss of prefoldin function leads to impaired solubility of cellular proteins. The degradation of proteins by the proteasome is an integral part of protein homeostasis. Failure of regulated protein degradation can lead to the accumulation of misfolded and defective proteins. We show that prefoldin subunit 5 is required for proteasome activity by contributing to the assembly of the 26S proteasome. In particular, we found that the absence of prefoldin subunit 5 impairs the formation of the Rpt ring subcomplex of the proteasome. Concomitant deletion of PFD5 and HSM3, a chaperone for assembly of the ATPase subunits comprising the Rpt ring, exacerbates this effect, suggesting a synergistic relationship between the two factors in proteasome assembly. Thus, our findings reveal a regulatory mechanism wherein prefoldin subunit 5 plays a crucial role in maintaining proteasome integrity, thereby influencing the degradation of proteins.

molecular biology↗

bioRxiv2023

Analysis of ageing-dependent thiol oxidation reveals early oxidation of proteins involved in core proteostasis functions

Oxidants have a profound impact on biological systems in physiology and under pathological conditions. Oxidative post-translational modifications of protein thiols are well-recognized as a readily occurring alteration of proteins. Changes in protein thiol redox state can modify the function of proteins and thus can control cellular processes. However, chronic oxidative stress causes oxidative damage to proteins with detrimental consequences for cellular function and organismal health. The development of techniques enabling the site-specific and quantitative assessment of protein thiol oxidation on a proteome-wide scale significantly expanded the number of known oxidation-sensitive protein thiols. However, lacking behind are large-scale data on the redox state of proteins during ageing, a physiological process accompanied by increased levels of endogenous oxidants. Here, we present the landscape of protein thiol oxidation in chronologically aged wild-type Saccharomyces cerevisiae in a time-dependent manner. Our data determine early oxidation targets in key biological processes governing the de novo production of proteins, folding, and protein degradation. Comparison to existing datasets reveals evolutionary conservation of early oxidation targets. To facilitate accessibility and cross-species comparison of the experimental data obtained, we created the OxiAge Database, a free online tool for the research community that integrates current datasets on thiol redoxomes in aged yeast, nematode Caenorhabditis elegans, fruit fly Drosophila melanogaster, and mouse Mus musculus. The database can be accessed through an interactive web application at http://oxiage.ibb.waw.pl.

molecular biology↗