Deoxynivalenol triggers mitotic catastrophe and apoptosis in C2C12 myoblasts.

Deoxynivalenol (DON), commonly known as vomitoxin, is a mycotoxin produced by fungi and is frequently found as a contaminant in various cereal-based food worldwide. While the harmful effects of DON have been extensively studied in different tissues, its specific impact on the proliferation of skeletal muscle cells remains unclear. In this study, we utilized murine C2C12 myoblasts as a model to explore the influence of DON on their proliferation. Our observations indicated that DON exhibits dose-dependent toxicity, significantly inhibiting the proliferation of C2C12 cells. Through the application of RNA-seq analysis combined with gene set enrichment analysis, we identified a noteworthy downregulation of genes linked to the extracellular matrix (ECM) and condensed chromosome. Concurrently with the reduced expression of ECM genes, immunostaining analysis revealed notable changes in the distribution of fibronectin, a vital ECM component, condensing into clusters and punctate formations. Remarkably, the exposure to DON induced the formation of multipolar spindles, leading to the disruption of the normal cell cycle. This, in turn, activated the p53-p21 signaling pathway and ultimately resulted in apoptosis. These findings contribute significant insights into the mechanisms through which DON induces toxicity within skeletal muscle cells.

SRSF1 Is Required for Mitochondrial Homeostasis and Thermogenic Function in Brown Adipocytes Through its Control of Ndufs3 Splicing.

RNA splicing dysregulation and the involvement of specific splicing factors are emerging as common factors in both obesity and metabolic disorders. The study provides compelling evidence that the absence of the splicing factor SRSF1 in mature adipocytes results in whitening of brown adipocyte tissue (BAT) and impaired thermogenesis, along with the inhibition of white adipose tissue browning in mice. Combining single-nucleus RNA sequencing with transmission electron microscopy, it is observed that the transformation of BAT cell types is associated with dysfunctional mitochondria, and SRSF1 deficiency leads to degenerated and fragmented mitochondria within BAT. The results demonstrate that SRSF1 effectively binds to constitutive exon 6 of Ndufs3 pre-mRNA and promotes its inclusion. Conversely, the deficiency of SRSF1 results in impaired splicing of Ndufs3, leading to reduced levels of functional proteins that are essential for mitochondrial complex I assembly and activity. Consequently, this deficiency disrupts mitochondrial integrity, ultimately compromising the thermogenic capacity of BAT. These findings illuminate a novel role for SRSF1 in influencing mitochondrial function and BAT thermogenesis through its regulation of Ndufs3 splicing within BAT.