Fig. 10.

Regulation of TRPML1 channel activity and inflammatory exosome release by endogenously produced ROS in mouse podocytes. In response to Hcy, NADPH oxidase is activated to produce ROS in podocytes. NLRP3 inflammasomes are activated by ROS to produce inflammatory cytokines such as IL-1β, which enter the late endosomes that form MVBs. At the same time, lysosomal Ca²⁺ release through TRPML1 channel is inhibited by ROS, leading to the impairment of lysosome trafficking and reduction of lysosome-MVB interaction, a process determining the MVB fate. Under such conditions, decreased lysosome degradation of MVBs leads to robust release of MVB contents as inflammatory exosomes from podocytes. Hcy, homocysteine; NOX, NADPH oxidase; ROS, reactive oxygen species; MVB; multivesicular body.