Post-Translational Modification of Cysteines: A Key Determinant of Endoplasmic Reticulum-Mitochondria Contacts (MERCs)

Abstract

Cells must adjust their redox state to an ever-changing environment that could otherwise result in compromised homeostasis. An obvious way to adapt to changing redox conditions depends on cysteine post-translational modifications (PTMs) to adapt conformation, localization, interactions and catalytic activation of proteins. Such PTMs should occur preferentially in the proximity of oxidative stress sources. A particular concentration of these sources is found near membranes where the endoplasmic reticulum (ER) and the mitochondria interact on domains called MERCs (Mitochondria-Endoplasmic Reticulum Contacts). Here, fine inter-organelle communication controls metabolic homeostasis. MERCs achieve this goal through fluxes of Ca²⁺ ions and inter-organellar lipid exchange. Reactive oxygen species (ROS) that cause PTMs of mitochondria-associated membrane (MAM) proteins determine these intertwined MERC functions. Chronic changes of the pattern of these PTMs not only control physiological processes such as the circadian clock but could also lead to or worsen many human disorders such as cancer and neurodegenerative diseases.

Keywords: cysteines; endoplasmic reticulum; mitochondria; redox.