Frontiers in cell death最新文献

When yeast cells are transferred to water only, they remain viable for several days. However, when transferred to water with glucose, there is a rapid loss of viability. This phenomenon is termed Sugar-Induced Cell Death (SICD). In addition to glucose, SICD can be induced by an array of different sugars and is thought to be triggered by increased levels of intracellular reactive oxygen species (ROS) generated upon transfer to sugar-only solutions. Although not termed SICD, a similar response is observed in mammalian cells, whereby high glucose induces cell death, especially in cases of hyperglycemia and diabetes. In contrast, cancer cells thrive under conditions of high glucose. In this review, we summarize the current understanding of SICD in yeast and highlight studies showing the presence of a similar phenomenon in mammalian cells, High Glucose-Induced Cell Death (HGICD). We end with a discussion on mechanisms by which cancer cells evade HGICD. Unlike other types of cell death in yeast, SICD has not yet been thoroughly reviewed. Therefore, this review represents the first comprehensive review of SICD in yeast with a comparison to HGICD in other eukaryotes.

Glucose deprivation (GD), a common metabolic stress condition, has been recognized as a potent inducer of necroptotic cell death. Our previous findings suggested that the mitochondrial protein, Noxa, may be involved in mediating the release of mitochondrial DNA during GD-induced ZBP1-dependent necroptotic pathway. However, the functional significance of Noxa in necroptosis under GD treatment remains unclear. Here, we investigated the role of Noxa in GD-induced necroptosis and the underlying molecular mechanisms governing its expression. We revealed that Noxa is required for the induction of necroptosis under GD. We also demonstrated that the upregulation of Noxa induced by GD is mediated by ATF4, a key transcription factor. These results provide insights into the regulatory mechanisms underlying Noxa dynamics during GD treatment and highlights its potential as a therapeutic target in cancer therapy and necroptosis-related diseases.

The pro-inflammatory form of cellular death, necroptosis, is critical to age-related pathologies. Necroptosis primarily functions as an antipathogenic and antitumor biological mechanism by triggering inflammatory pathways within rogue cell bodies, resulting in cell death. Several neurodegenerative conditions have hallmarks of necroptosis, suggesting a potential role for this cell death pathway in the pathogenesis of neuroinflammation and neuronal cell death, likely through the release of pro-inflammatory cytokines that perpetuate inflammatory signaling and neurodegeneration. The receptor-interacting protein kinases 1 and 3 (RIPK1/3) signaling cascade is critical to necroptosis regulation; however, the complete mechanism behind necroptotic activation, regulation, and resolution remains incomplete. In cases where necroptosis is disadvantageous, such as neurodegenerative diseases, we lack effective pharmacological suppressors of necroptosis that could mitigate disease progression. Targeting regulatory proteins within the necroptotic signaling pathway has shown promise; however, the need for specific inhibitors limits therapeutic opportunities. This review focuses on necroptosis and its role in neuroinflammation and neurodegeneration in age-dependent disorders. We comprehensively detail the known necroptotic signaling pathways and potential signaling partners and discuss the ongoing therapeutic efforts in targeting and preventing active necroptotic signaling and their relevance to neuroprotection.

We conducted an EMS mutagenesis screen on chromosome arm 2L to identify recessive suppressors of GMR-hid-induced apoptosis in the Drosophila eye. Through this screen, we recovered three alleles of the lysine demethylase gene Kdm5. Kdm5, a member of the JmjC-domain-containing protein family, possesses histone demethylase activity towards H3K4me3. Our data suggest that Kdm5 specifically regulates Hid-induced cell death during development, as we did not observe control of Reaper- or Grim-induced cell death by Kdm5. Interestingly, GMR-hid-induced apoptosis is suppressed independently of Kdm5's demethylase activity. Our findings indicate that Rbf and dMyc are necessary for Kdm5 mosaics to suppress GMR-hid-induced cell death. Moreover, Kdm5 mosaics failed to suppress apoptosis induced by a mutant form of Hid that is resistant to inhibition by Erk-type MAPK activity. Additionally, Kdm5 dominantly enhances the wing phenotype of an activated MAPK mutant. These results collectively suggest that Kdm5 controls Hid-induced apoptosis by regulating the Rbf, dMyc, and MAPK pathways.