Fig. 9. Mechanism underlying paraptosis.

Paraptosis is characterized by the development of large vacuoles in the endoplasmic reticulum (ER) and mitochondria, ultimately leading to the formation of large cytoplasmic vacuoles. Impaired proteostasis, altered ion homeostasis, and ER stress cause paraptosis, resulting in the discharge of Ca²⁺ from the ER and accumulation of Ca²⁺ in mitochondria. Paraptosis can be facilitated by the activation of mitogen-activated protein kinase (MAPK) signaling pathways via IGF-IR and inhibited by AIP-1/Alix.