ER-Mitochondria Calcium Transfer, Organelle Contacts and Neurodegenerative Diseases

It is generally accepted that interorganellar contacts are central to the 7 control of cellular physiology. Virtually, any intracellular organelle can come into 8 proximity with each other and, by establishing physical protein-mediated contacts 9 within a selected fraction of the membrane surface, novel specific functions are 10 acquired. Endoplasmic reticulum (ER) contacts with mitochondria are among the 11 best studied with major roles in Ca2+ and lipid transfer, signaling, and membrane 12 dynamics. 13 This functional (and structural) diversity, their dynamic nature as well as the 14 growing number of new players concurred to make their monitoring difficult. 15 This review focuses on the most established examples of tethers/modulators of 16 the ER-mitochondria interface and on the roles of these contacts in health and 17 disease by specifically dissecting how Ca2+ transfer occur and how mishandling 18 eventually lead to disease. Additional functions of the ER-mitochondria interface 19 and an overview of the currently available methods to measure/quantify the ER- 20 mitochondria interface will also be considered.