Protein Localization at Mitochondria-ER Contact Sites in Basal and Stress Conditions

Mitochondria-endoplasmic reticulum (ER) contacts (MERCs) are sites at which the outer mitochondria membrane and the Endoplasmic Reticulum surface run in parallel at a constant distance. The juxtaposition between these organelles determines several intracellular processes such as to name a few, Ca2+ and lipid homeostasis or autophagy. These specific tasks can be exploited thanks to the enrichment (or re-localization) of dedicated proteins at these interfaces. Recent proteomic studies highlight the tissue specific composition of MERCs, but the overall mechanisms that control MERCs plasticity remains unclear. Understanding how proteins are targeted at these sites seems pivotal to clarify such contextual function of MERCs. This review aims to summarize the current knowledge on protein localization at MERCs and the possible contribution of the mislocalization of MERCs components to human disorders.This work was supported by CARIPARO Starting Grant 2016 AIFbiol (toMG) and DiBio Departmental Research Project PRID Seed 2017 (to MG); MD received support from grants SAF201451876-R from MINECO (Spanish Ministry of Economy and Competitiveness) and 15-0404 from the Worldwide Cancer Research Foundation. MS-Á is recipient of an IPP-CNIC postdoctoral fellow award. The CNIC is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S