3,3’-Diindolylmethane induces apoptosis and autophagy in fission yeast

Abstract

Abstract3,3’-Diindolylmethane (DIM) is a compound derived from the digestion of indole-3-carbinol, found in the broccoli family. It induces apoptosis and autophagy in some types of human cancer. DIM extends lifespan in the fission yeast Schizosaccharomyces pombe. The mechanisms by which DIM induces apoptosis and autophagy in humans and expands lifespan in fission yeasts are not fully understood. Here, we show that DIM induces apoptosis and autophagy in log-phase cells, which is dose-dependent in fission yeast. A high concentration of DIM disrupted the nuclear envelope (NE) structure and induced chromosome condensation at an early time point. In contrast, a low concentration of DIM induced autophagy but did not disrupt NE structure. The mutant defective in autophagy was more sensitive to a low concentration of DIM, demonstrating that the autophagic pathway contributes to the survival of cells against DIM. Moreover, our results showed that the lem2 mutant is more sensitive to DIM. NE in the lem2 mutant was disrupted even at the low concentration of DIM. Our results demonstrate that the autophagic pathway and NE integrity are important to maintain viability in the presence of a low concentration of DIM. The mechanism of apoptosis and autophagy induction by DIM might be conserved in fission yeast and humans. Further studies will contribute to the understanding of the mechanism of apoptosis and autophagy by DIM in fission yeast and humans.

Sporulation: A response to starvation in the fission yeast Schizosaccharomyces pombe

“…In yeast, the survival rate after entry into the stationary phase is measured as the CLS (Kurauchi et al, 2017; Legon & Rallis, 2022; Lin & Austriaco, 2014; Longo et al, 2012; Matsui et al, 2021; Roux et al, 2010). At least 100 genes, 30 drugs, and approximately 10 nutritional conditions have extended the CLS in S. pombe (Emami & Ueno, 2021; Fujita et al, 2007; Hibi et al, 2018; Imai et al, 2020; Naito et al, 2014; Ohtsuka et al, 2021c; Romila et al, 2021; Su et al, 1996; Takuma et al, 2013). Therefore, a comprehensive understanding of CLS requires a detailed review of the biology and molecular mechanisms involved in the lifecycle of S. pombe .…”

Tetraconazole-induced Programmed Cell Death in Schizosaccharomyces pombe

“…However, cellular physiology of yeast apoptosis is not fully understood and waiting to be unraveled [36]. Whereas oxidative stress [25], mitochondrial impairment and lipotoxicity are well-known stimulations for the positive regulation of apoptosis in yeast, we do not know much about the dark side of the genetic regulation [37]. Indeed, many genes (caspases and endonucleases) having potential roles in apoptosis of Baker's yeast (S. cerevisiae) were investigated [38],however, the orthologous genes (at least several of them) in the fission yeast (S. pombe)are waiting to be enlightened.…”