Selenoprotein o as a regulator of macrophage metabolism in selenium deficiency-induced lung inflammation.

Selenium (Se) deficiency induces an inflammatory response in the lungs, but the underlying mechanisms are unknown. Selenoprotein O (SelO) is the largest selenoprotein in terms of molecular weight, yet its potential biological functions have yet to be characterized. Our study revealed that Se deficiency leads to an imbalance in the expression of pro-inflammatory "M1" macrophages and anti-inflammatory "M2" macrophages in alveolar macrophages (AMs) and interstitial macrophages (IMs) and contributed to the development of lung inflammation. Through the analysis of differentially expressed selenoproteins, we identified SelO as a potential regulator of the imbalance in pulmonary macrophage polarization caused by Se deficiency. In vitro experiments showed that SelO knockdown enhanced the polarization of M1 macrophages while suppressing that of M2 macrophages. In addition, SelO knockdown reprogrammed macrophage metabolism to glycolysis, disrupting oxidative phosphorylation (OXPHOS). Mechanistically, SelO primarily targets mitochondrial transcription factor A (TFAM), which plays a crucial role in the transcription and replication of mitochondrial DNA (mtDNA) and is essential for mitochondrial biogenesis and energy metabolism. The deficiency of SelO affects TFAM, resulting in its uncontrolled degradation, which compromises mitochondrial function and energy metabolism. In summary, the findings presented here offer significant theoretical insights into the physiological functions of SelO.

Redefining pseudokinases: A look at the untapped enzymatic potential of pseudokinases.

Catalytically inactive kinases, known as pseudokinases, are conserved in all three domains of life. Due to the lack of catalytic residues, pseudokinases are considered to act as allosteric regulators and scaffolding proteins with no enzymatic function. However, since these "dead" kinases are conserved along with their active counterparts, a role for pseudokinases may have been overlooked. In this review, we will discuss the recently characterized pseudokinases Selenoprotein O, Legionella effector SidJ, and the SARS-CoV2 protein nsp12 which catalyze AMPylation, glutamylation, and RNAylation, respectively. These studies provide structural and mechanistic insight into the versatility and diversity of the kinase fold.

SELENOPROTEIN O is a chloroplast protein involved in ROS scavenging and its absence increases dehydration tolerance in Arabidopsis thaliana.

The evolutionary conserved family of Selenoproteins performs redox-regulatory functions in bacteria, archaea and eukaryotes. Among them, members of the SELENOPROTEIN O (SELO) subfamily are located in mammalian and yeast mitochondria, but their functions are thus far enigmatic. Screening of T-DNA knockout mutants for resistance to the proline analogue thioproline (T4C), identified mutant alleles of the plant SELO homologue in Arabidopsis thaliana. Absence of SELO resulted in a stress-induced transcriptional activation instead of silencing of mitochondrial proline dehydrogenase, and also high elevation of Δ(1)-pyrroline-5-carboxylate dehydrogenase involved in degradation of proline, thereby alleviating T4C inhibition and lessening drought-induced proline accumulation. Unlike its animal homologues, SELO was localized to chloroplasts of plants ectopically expressing SELO-GFP. The protein was co-fractionated with thylakoid membrane complexes, and co-immunoprecipitated with FNR, PGRL1 and STN7, all involved in regulating PSI and downstream electron flow. The selo mutants displayed extended survival under dehydration, accompanied by longer photosynthetic activity, compared with wild-type plants. Enhanced expression of genes encoding ROS scavenging enzymes in the unstressed selo mutant correlated with higher oxidant scavenging capacity and reduced methyl viologen damage. The study elucidates SELO as a PSI-related component involved in regulating ROS levels and stress responses.

Selenoprotein O deficiencies suppress chondrogenic differentiation of ATDC5 cells.

Selenoprotein O (Sel O) is a selenium-containing protein, but its function is still unclear. In the present study, we observed that the mRNA and protein expression levels of Sel O increased during chondrogenic induction of ATDC5 cells. The effects of Sel O on chondrocyte differentiation were then examined through shRNA-mediated gene silencing technique. The expression of Sel O was significantly suppressed at both mRNA and protein levels in a stable cell line transfected with a Sel O-specific target shRNA construct. Thereafter, we demonstrated that Sel O deficiencies suppress chondrogenic differentiation of ATDC5 cells. Sel O deficiencies inhibited expression of chondrogenic gene Sox9, Col II, and aggrecan. Sel O-deficient cells also accumulated a few cartilage glycosaminoglycans (GAGs) and decreased the activity of alkaline phosphatase (ALP). In addition, Sel O deficiencies inhibited chondrocyte proliferation through delayed cell cycle progression by suppression of cyclin D1 expression. Moreover, Sel O deficiencies induced chondrocyte death through cell apoptosis. In summary, we describe the expression patterns and the essential roles of Sel O in chondrocyte viability, proliferation, and chondrogenic differentiation. Additionally, Sel O deficiency-mediated impaired chondrogenesis may illustrate the mechanisms of Se deficiency in the pathophysiological process of the endemic osteoarthropathy.