Figure 1.

Schematic representation of the crosstalk between autophagy, endoplasmic reticulum, and inflammation in neurons mediated by Klotho depletion.

Under endoplasmic reticulum (ER) stress, the inflammatory response is activated by mitochondria-released reactive oxygen species (ROS) and enhanced secretion of proinflammatory cytokines. As feedback, ER stress could be further accelerated by an inflammatory response. On the other hand, inflammation could be inhibited by autophagy triggered by ER. In response, autophagy-mediated degradation of inflammatory-related proteins and mitochondrial turnover could inhibit ER stress. Although Klotho seems to be engaged in all processes, its role is probably limited to being a molecular switch on the line “die” (cell death) or “survive” (cell survival). Klotho^–: Klotho depletion.