Oxidative stress is characterized by an excessive concentration of reactive oxygen species (ROS) resulting from a disturbance in the balance between ROS production and their removal by antioxidant systems (SOD, CAT, GPx). Prolonged and intense oxidative stress can cause various forms of damage to cells, which markers are total antioxidant capacity (TAC), reactive oxygen species modulator (ROMO1), and malondialdehyde (MDA). It has been demonstrated that magnetic fields can positively affect human health, for example, by reducing oxidative stress. Determination of the effect of a rotating magnetic field (RMF) on the activity/concentration of selected oxidative stress markers. A group of 30 healthy volunteers (15 women and 15 men) (mean age 24.8 ± 5.1) in the study classified into the following groups: internal control group (CG);1 h 25 Hz (samples placed in the field for one hour at 25 Hz); 3 h 25 Hz (samples placed in the field for 3 h at 25 Hz), the 1 h 50 Hz group ( placed in RMF for an hour at 50 Hz), and a group of 3 h 50 Hz (samples placed in the field for 3 h at 50 Hz). Serum samples were collected in K2EDTA tubes.. The magnetic induction value obtained for RMF is 37.06 mT and 42.64 mT.Activity/concentration of selected oxidative stress markers was analyzed by ELISA. The influence of an RMF on the activity/concentration of SOD, MDA, TAC, and ROMO1 was demonstrated (p < 0.001; p = 0.0013; p < 0.001; p = 0.003). The RFM can reduce oxidative stress, as evidenced by higher SOD and CAT activities in the CG than in samples placed in the RFM. Prolonged exposure to the RFM at 50 Hz increased the TAC level, indicating an intensification of oxidative stress in these samples. The optimal conditions for staying in the RFM (reducing oxidative stress) are 1 h 50 Hz for SOD and MDA; 3 h 25 Hz for CAT and TAC. In the case of ROMO1, it is stated that 1 h 25 Hz are the optimal conditions for no increased production of ROS.

OBJECTIVE: Due to the complexity of drug-induced lupus (DIL) pathogenesis, more susceptibility factors need to be discovered. FAM210B is a new mitochondrial protein whose function has not been fully elucidated. This study will explore whether there is a correlation between FAM210B and the risk of DIL.
METHODS: At first, we extracted three FAM210B genetic variants from the GTEx database (n = 948), and extracted their corresponding genome-wide association study (GWAS) summary statistics from DIL (101 DIL cases and 218691 controls). Then, we performed a Mendelian randomization (MR) study to evaluate the causal association of the expression of FAM210B with DIL using inverse-variance weighted (IVW), the weighted median, MR-Egger, and MR-PRESSO test.
RESULTS: We successfully extracted three FAM210B single-nucleotide polymorphisms (SNPs) (rs116032784, rs34361943 and rs33923703) from the GTEx_Analysis_v8_eQTL data that can reduce FAM210B expression. The results of the MR analysis showed that genetically reduced expression of FAM210B was significantly associated with increased risk of DIL in European ancestry based on the IVW method (β = 1.037, p = 0.001, odds ratio [OR] = 2.821, 95% confidence interval [CI]:1.495-5.322).
CONCLUSIONS: MR analysis showed a causal relationship between FAM210B expression and the risk of DIL disease. Our results suggested that FAM210B may be a marker that can mark susceptibility of DIL in the future. It provides evidence for the study of DIL, but its specific mechanism of action in DIL needs to be further studied. Key Points •This is the first MR analysis to examine the association between FAM210B and DIL. •The findings of this study suggested that reduced FAM210B expression is associated with the increased risk of DIL. •FAM210B may be a marker that can mark susceptibility of DIL in the future.

OBJECTIVE: This study systematically assessed circulating proteins to identify new serum biomarkers and risk of hypertension using Mendelian randomisation.
METHODS: The associations between 4,782 human circulating proteins and the risk of hypertension were evaluated using two-sample Mendelian randomisation. The FinnGen study demonstrated a link between genetic predisposition and hypertension in 85,438 cases and 223,663 controls.
RESULTS: Inverse variance weighted and sensitivity analysis revealed nine proteins in circulation that have a causative effect on hypertension. SMOC1 and TIE1 were determined to be causative factors in the decreased likelihood of developing hypertension, with odds ratios of 0.86 (95% CI 0.81-0.91; p=1.06e-06) and 0.96 (95% CI 0.94-0.98; p=9.39e-05), respectively. NDUFB4, ETHE1, POFUT2, TRIL, ADAM23, GXYLT1, OXT, TPST2, and TMCC3 showed a possible connection to hypertension.
CONCLUSIONS: This two-sample Mendelian randomisation study found that SMOC1 and TIE1 are causally linked to hypertension, making them a promising target for therapy.

BACKGROUND: Atabecestat, a potent brain penetrable BACE1 inhibitor that reduces CSF amyloid beta (Aβ), was developed as an oral treatment for Alzheimer\'s disease (AD). Elevated liver enzyme adverse events were reported in three studies although only one case met Hy\'s law criteria to predict serious hepatotoxicity.
METHODS: We performed a case-control genome-wide association study (GWAS) to identify genetic risk variants associated with liver enzyme elevation using 42 cases with alanine transaminase (ALT) above three times the upper limit of normal (ULN) and 141 controls below ULN. Additionally, we performed a GWAS using continuous maximal ALT/ULN (expressed as times the ULN) upon exposure to atabecestat as the outcome measure (n = 285).
RESULTS: No variant passed the genome-wide significance threshold (p = 5 × 10- 8) in the case-control GWAS. We identified suggestive association signals in genes (NLRP1, SCIMP, and C1QBP) implicated in the inflammatory processes. Among the genes implicated by position mapping using variants suggestively associated (p < 1 × 10- 5) with ALT elevation case-control status, gene sets involved in innate immune response (adjusted p-value = 0.05) and regulation of cytokine production (adjusted p-value = 0.04) were enriched. One genomic region in the intronic region of GABRG3 passed the genome-wide significance threshold in the continuous max(ALT/ULN) GWAS, and this variant was nominally associated with ALT elevation case status (p = 0.009).
CONCLUSIONS: The suggestive GWAS signals in the case-control GWAS analysis suggest the potential role of inflammation in atabecestat-induced liver enzyme elevation.

This is the first study to identify 23 protein spots corresponding to 13 proteins in mitochondria isolated from rabbit epididymal spermatozoa. In the group of protein spots identified in stress-induced samples, the abundance of 20 protein spots increased, whereas the abundance of three protein spots (GSTM3, CUNH9orf172, ODF1) decreased relative to the control. The results of this study provide valuable inputs for future research into the molecular mechanisms implicated in pathological processes during oxidative stress (OS).

Biotin-based proximity labeling approaches, such as BioID, have demonstrated their use for the study of mitochondria proteomes in living cells. The use of genetically engineered BioID cell lines enables the detailed characterization of poorly characterized processes such as mitochondrial co-translational import. In this process, translation is coupled to the translocation of the mitochondrial proteins, alleviating the energy cost typically associated with the post-translational import relying on chaperone systems. However, the mechanisms are still unclear with only few actors identified but none that have been described in mammals yet. We thus profiled the TOM20 proxisome using BioID, assuming that some of the identified proteins could be molecular actors of the co-translational import in human cells. The obtained results showed a high enrichment of RNA binding proteins close to the TOM complex. However, for the few selected candidates, we could not demonstrate a role in the mitochondrial co-translational import process. Nonetheless, we were able to demonstrate additional uses of our BioID cell line. Indeed, the experimental approach used in this study is thus proposed for the identification of mitochondrial co-translational import effectors and for the monitoring of protein entry inside mitochondria with a potential application in the prediction of mitochondrial protein half-life.

Dual localization or dual targeting refers to the phenomenon by which identical, or almost identical, proteins are localized to two (or more) separate compartments of the cell. From previous work in the field, we had estimated that a third of the mitochondrial proteome is dual-targeted to extra-mitochondrial locations and suggested that this abundant dual targeting presents an evolutionary advantage. Here, we set out to study how many additional proteins whose main activity is outside mitochondria are also localized, albeit at low levels, to mitochondria (eclipsed). To do this, we employed two complementary approaches utilizing the α-complementation assay in yeast to uncover the extent of such an eclipsed distribution: one systematic and unbiased and the other based on mitochondrial targeting signal (MTS) predictions. Using these approaches, we suggest 280 new eclipsed distributed protein candidates. Interestingly, these proteins are enriched for distinctive properties compared to their exclusively mitochondrial-targeted counterparts. We focus on one unexpected eclipsed protein family of the Triose-phosphate DeHydrogenases (TDH) and prove that, indeed, their eclipsed distribution in mitochondria is important for mitochondrial activity. Our work provides a paradigm of deliberate eclipsed mitochondrial localization, targeting and function, and should expand our understanding of mitochondrial function in health and disease.

UNASSIGNED: Based on hypothetical hypothyroidism and nonthyroidal illness syndrome (NTIS) gene expression similarities, we decided to compare the patterns of expression of both as models of NTIS. The concordant profile between them may enlighten new biomarkers for NTIS challenging scenarios.
UNASSIGNED: We used Ion Proton System next-generation sequencing to build the hypothyroidism transcriptome. We selected two databanks in GEO2 platform datasets to find the differentially expressed genes (DEGs) in adults and children with sepsis. The ROC curve was constructed to calculate the area under the curve (AUC). The AUC, chi-square, sensitivity, specificity, accuracy, kappa and likelihood were calculated. We performed Cox regression and Kaplan-Meier analyses for the survival analysis.
UNASSIGNED: Concerning hypothyroidism DEGs, 70.42% were shared with sepsis survivors and 61.94% with sepsis nonsurvivors. Some of them were mitochondrial gene types (mitGenes), and 95 and 88 were related to sepsis survivors and nonsurvivors, respectively. BLOC1S1, ROMO1, SLIRP and TIMM8B mitGenes showed the capability to distinguish sepsis survivors and nonsurvivors.
UNASSIGNED: We matched our hypothyroidism DEGs with those in adults and children with sepsis. Additionally, we observed different patterns of hypothyroid-related genes among sepsis survivors and nonsurvivors. Finally, we demonstrated that ROMO1, SLIRP and TIMM8B could be predictive biomarkers in children´s sepsis.

Mitochondrial translation is an intricate process involving both general and mRNA-specific factors. In addition, in the yeast Saccharomyces cerevisiae, translation of mitochondrial mRNAs is coupled to assembly of nascent polypeptides into the membrane. ARG8m is a reporter gene widely used to study the mechanisms of yeast mitochondrial translation. This reporter is a recodified gene that uses the mitochondrial genetic code and is inserted at the desired locus in the mitochondrial genome. After deletion of the endogenous nuclear gene, this reporter produces Arg8, an enzyme necessary for arginine biosynthesis. Since Arg8 is a soluble protein with no relation to oxidative phosphorylation, it is a reliable reporter to study mitochondrial mRNAs translation and dissect translation form assembly processes. In this chapter, we explain how to insert the ARG8m reporter in the desired spot in the mitochondrial DNA, how to analyze Arg8 synthesis inside mitochondria, and how to follow steady-state levels of the protein. We also explain how to use it to find spontaneous suppressors of translation defects.

To understand the human mitochondrial translation process, tools are required to dissect this system at a global scale. The mechanisms and regulation of translation in mitochondria are different from those in the cytosol, and mitochondrial ribosomes have distinct biochemical properties. In this chapter, we describe in detail the modifications we have made to the ribosome profiling approach to adapt it to the unique characteristics of the human mitochondrial ribosome. This approach maximizes the fraction of mitochondrial ribosomes recovered, providing a snapshot of the mitochondrial translation landscape with minimal bias. We also describe the use of mouse lysate as an internal spike-in control for normalization, allowing quantification of global changes in translation across samples. Finally, we outline the bioinformatic pipelines to process the raw reads and identify mitoribosome A sites in the absence of untranslated regions flanking open reading frames. This method offers a subcodon-resolution time-sensitive global approach to explore the mitochondrial translation process in human cells.