Rbm46 inhibits reactive oxygen species in mouse embryonic stem cells through modulating BNIP3-mediated mitophagy.

Embryonic stem cells (ESCs) exhibit a metabolic preference for glycolysis over oxidative phosphorylation to meet their substantial adenosine triphosphate (ATP) demands during self-renewal. This metabolic choice inherently maintains low mitochondrial activity and minimal reactive oxygen species (ROS) generation. Nonetheless, the intricate molecular mechanisms governing the restraint of ROS production and the mitigation of cellular damage remain incompletely elucidated. In this study, we reveal the pivotal role of RNA-binding motif protein 46 (RBM46) in ESCs, acting as a direct post transcriptional regulator of ROS levels by modulating BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (Bnip3) mRNA expression. Rbm46 knockout lead to diminished mitochondrial autophagy, culminating in elevated ROS within ESCs, disrupting the delicate balance required for healthy self-renewal. These findings provide insights into a novel mechanism governing ROS regulation in ESCs.

Targeting dysregulated phago-/auto-lysosomes in Sertoli cells to ameliorate late-onset hypogonadism.

Age-related changes in testicular function can impact health and well-being. The mechanisms underlying age-related testicular dysfunction, such as late-onset hypogonadism (LOH), remain incompletely understood. Using single-cell RNA sequencing on human testes with LOH, we delineated Sertoli cells (SCs) as pivotal metabolic coordinators within the testicular microenvironment. In particular, lysosomal acidity probing revealed compromised degradative capacity in aged SCs, hindering autophagy and phagocytic flux. Consequently, SCs accumulated metabolites, including cholesterol, and have increased inflammatory gene expression; thus, we termed these cells as phago-/auto-lysosomal deregulated SCs. Exposure to a high-fat diet-induced phago-/auto-lysosomal dysregulated-like SCs, recapitulating LOH features in mice. Notably, efferent ductular injection and systemic TRPML1 agonist administration restored lysosomal function, normalizing testosterone deficiency and associated abnormalities in high-fat diet-induced LOH mice. Our findings underscore the central role of SCs in testis aging, presenting a promising therapeutic avenue for LOH.

Release of tetrabromobisphenol A (TBBPA)-derived non-extractable residues in oxic soil and the effects of the TBBPA-degrading bacterium Ochrobactrum sp. strain T.

Tetrabromobisphenol A (TBBPA) forms large amount of non-extractable residues (NER) in soil. However, the stability of TBBPA-NER with TBBPA degrader in soil had not been determined. In this study, a 14C-tracer was used to follow the release and alteration of TBBPA-derived NER during 214 days of incubation in oxic soil and in the presence or absence of the TBBPA-degrading bacterium Ochrobatrum sp. strain T. In the absence of strain T, 1.89% of the TBBPA and its metabolites were slowly released from the NER, with TBBPA as the predominant component, accompanied by 2.47% mineralization by day 91 of the incubation. The addition of active cells strongly stimulated the release and mineralization of NER (10.93% and 4.64%, respectively), reduced the amount of the ester-linked fraction, and transformed NER from humin-bound to HA-bound forms. Cells added to the soil in sterilized form had much smaller effects on the stability and internal alterations of NER. Among the ester-linked compounds, 47.4% consisted of TBBPA; two metabolites were so detected. These results provide new information on the stability and internal transformation of TBBPA-NER in soil during its long-term incubation and underlines the importance of microbial TBBPA degraders in determining the composition of NER in soil.