Biology subjects

Radkiewicz, M.

Publications and source records attributed to Radkiewicz, M..

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↗

bioRxiv2025

LOSS OF ARGINASE 2 DISRUPTS STRIATUM-SPECIFIC POLYAMINE HOMEOSTASIS

Arginase converts arginine (Arg) to ornithine (Orn), regulating their availability for the metabolic pathways that utilize these amino acids. The roles of arginase isoenzymes, Arg1 and Arg2, vary by cell type, tissue, and physiological state. In the brain, Arg2 is the predominant isoenzyme, particularly enriched in the striatum, where it localizes to a striatum-specific neuronal population - medium spiny neurons (MSNs). While the precise role of Arg2 in MSNs remains unclear, its loss alters the striatal metabolomic profile, highlighting its metabolic significance. Here, to investigate the basis of these complex metabolic changes, we examined Arg metabolism in Arg2 knockout (Arg2-/-) mice. Targeted analysis of Arg-related metabolites and selected proteins regulating Arg metabolic pathways revealed that Arg2 loss significantly increased Arg levels but did not affect Orn, likely due to compensatory synthesis of Orn from Arg (via arginine:glycine amidinotransferase) and/or proline (via ornithine aminotransferase). Additionally, markers of nitric oxide (NO) production remained unchanged, suggesting that striatal Arg2 is not involved in the regulation of this pathway, a role commonly attributed to arginase. Most notably, Arg2 loss disrupted polyamine homeostasis, shifting the balance toward higher polyamines at the expense of lower ones and altering the expression of polyamine-regulating proteins. These findings highlight Arg2 crucial role in striatal metabolism and its potential relevance to striatum-related disorders. Given that striatal Arg2 impairment has been reported in Huntingtons disease, a neurodegenerative disorder specifically affecting MSNs, understanding its function may provide insights into the pathology.

neuroscience↗

bioRxiv2024

Integrated proteome and lipidome analyses place OCIAD1 at mitochondria-peroxisome intersection balancing lipid metabolism

OCIAD1 (Ovarian Cancer Immunoreactive Antigen Domain Containing 1) is a membrane protein largely localized to mitochondria, however, its function in health or disease is not well understood. To comprehensively characterize the molecular changes upon lack of OCIAD1, we used mass spectrometry to study the mitochondrial and cellular proteome and lipidome. We find extensive lipidome rearrangement in OCIAD1 KO cells, characterized by two main phenotypes of decreased ether phospholipids and decreased phospholipids with an odd number of carbons. The lipidomic changes suggest alterations in peroxisomal lipid metabolism. At the same time, proteins responsible for mitochondrial fatty acid {beta} oxidation are significantly increased. Together with a global loss in peroxisomal proteins and a meta-analysis of proximity labeling data, this gives a function to the previously observed partial localization of OCIAD1 to peroxisomes. We suggest a role for OCIAD1 in balancing mitochondrial and peroxisomal lipid metabolism, and a direct impact on the key enzymes FAR1 and ACBD3. Summary StatementLipidomics and proteomics of mitochondrial fractions and whole cells lacking the membrane protein OCIAD1 suggest a role as a dually localized protein balancing mitochondrial and peroxisomal lipid metabolism.

cell biology↗