Search

The implications of nutrient starvation due to aging on the degeneration of the retinal pigment epithelium (RPE) is yet to be fully explored. We examined the involvement of AMPK activation in mitochondrial homeostasis and its relationship with the maintenance of a healthy mitochondrial population and epithelial characteristics of RPE cells under nutrient starvation. Nutrient starvation induced mitochondrial senescence, which led to the accumulation of reactive oxygen species (ROS) in RPE cells. As nutrient starvation persisted, RPE cells underwent pathological epithelial-mesenchymal transition (EMT) via the upregulation of TWIST1, a transcription regulator which is activated by ROS-induced NF-κB signaling. Enhanced activation of AMPK with metformin decelerated mitochondrial senescence and EMT progression through mitochondrial biogenesis, primed by activation of PGC1-α. Thus, by facilitating mitochondrial biogenesis, AMPK protects RPE cells from the loss of epithelial integrity due to the accumulation of ROS in senescent mitochondria under nutrient starvation. [BMB Reports 2023; 56(2): 84-89].

In contrast to highly specific sensor molecules of the innate immune system, the NLRP3 receptor detects a broad variety of danger signals including pathogens. Sensing triggers intracellular NLRP3 inflammasome complex assembly to induce an inflammatory response with the primary aim to eliminate pathogens. However, several of them have developed distinct strategies to hijack NLRP3-dependent immunity. In this issue of EMBO Reports, Zhang and colleagues demonstrate that reovirus infection of airway epithelial cells promotes EphA2-dependent phosphorylation of NLRP3 that impedes the recruitment of other inflammasome components necessary for its activation [1]. This potentially uncovers a mechanism that may lead to reduced viral clearance in the lung, eventually contributing to life-threatening respiratory disease., (© 2020 The Authors.)

A new study has identified the sophisticated communication between the gut microbiota and intestinal epithelial cells that controls diurnal variations in the secretion of corticosteroids in mice. The absence of gut bacteria disrupts this communication and contributes to hypertriglyceridaemia, hyperglycaemia and insulin resistance.

The contribution and order of polarity complexes and vesicular trafficking events during lumen formation remains obscure. Now, lumenogenesis in MDCK cell cysts is shown to require a Rab11a-Rabin8-Rab8a network that recruits Sec15A and Cdc42 and that promotes apical exocytosis by enlisting the Par complex and Sec8-Sec10 to an early apical membrane initiation site.

The epithelial-mesenchymal transition (EMT) occurs in pre-metastatic cancer cells and is also associated with the acquisition of stem-cell-like characteristics. A molecular link between EMT and stemness now emerges with the finding that Bmi1, a polycomb protein that promotes self-renewal of certain stem-cell populations, is a direct transcriptional target of the EMT inducer, Twist1.