Fig. 6: The role of ROS in paraptosis.

Paraptosis is characterized by cytoplasmic vacuolation, resulting from extensive dilation of the endoplasmic reticulum (ER) and mitochondria. Vacuole formation in paraptosis necessitates the activation of mitogen-activated protein kinases (MAPKs). The onset of paraptosis is driven by ROS generation, initiating ER stress and Ca²⁺ overload. In contrast, thioredoxin reductase 1 (TXNRD1) critically curtails paraptosis by diminishing ROS production. Additionally, the interplay between mitochondria-associated ER membranes (MAMs) and the coordination of Ca²⁺ flux from the ER to mitochondria stand out as pivotal factors in inducing oxidative metabolic stress during paraptotic cell death.