Apoptotic signals at the endoplasmic reticulum-mitochondria interface

Abstract

The maintenance of cellular homeostasis involves the participation of multiple organelles, such as the endoplasmic reticulum (ER) and mitochondria. Specifically, ER plays a key role in calcium (Ca²⁺) storage, lipid synthesis, protein folding, and assembly, while mitochondria are the "energy factories" and provide energy to drive intracellular processes. Hence, alteration in ER or mitochondrial homeostasis has detrimental effects on cell survival, being linked to the triggering of apoptosis, a programmed form of cell death. Besides, ER stress conditions affect mitochondria functionality and vice-versa, as ER and mitochondria communicate via mitochondria-associated ER membranes (MAMs) to carry out a number of fundamental cellular functions. It is not surprising, thus, that also MAMs perturbations are involved in the regulation of apoptosis. This chapter intends to accurately discuss the involvement of MAMs in apoptosis, highlighting their crucial role in controlling this delicate cellular process.

Keywords: Apoptosis; Bioenergetics; Calcium signaling; ER-mitochondria contact sites; MAMs; Organelle tethering.