학술논문
PERK recruits E-Syt1 at ER-mitochondria contacts for mitochondrial lipid transport and respiration.
Document Type
Article
Author
Sassano, Maria Livia; van Vliet, Alexander R.; Vervoort, Ellen; Van Eygen, Sofie; Van den Haute, Chris; Pavie, Benjamin; Roels, Joris; Swinnen, Johannes V.; Spinazzi, Marco; Moens, Leen; Casteels, Kristina; Meyts, Isabelle; Pinton, Paolo; Marchi, Saverio; Rochin, Leila; Giordano, Francesca; Felipe-Abrio, Blanca; Agostinis, Patrizia
Source
Subject
*LIPID transfer protein
*RESPIRATION
*MITOCHONDRIA
*MOLECULAR pathology
*LIPIDS
*MEMBRANE lipids
*HOMEOSTASIS
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Language
ISSN
0021-9525
Abstract
The integrity of ER-mitochondria appositions ensures transfer of ions and phospholipids (PLs) between these organelles and exerts crucial effects on mitochondrial bioenergetics. Malfunctions within the ER-mitochondria contacts altering lipid trafficking homeostasis manifest in diverse pathologies, but the molecular effectors governing this process remain illdefined. Here, we report that PERK promotes lipid trafficking at the ER-mitochondria contact sites (EMCS) through a nonconventional, unfolded protein response-independent, mechanism. PERK operates as an adaptor for the recruitment of the ER-plasma membrane tether and lipid transfer protein (LTP) Extended-Synaptotagmin 1 (E-Syt1), within the EMCS. In resting cells, the heterotypic E-Syt1-PERK interaction endorses transfer of PLs between the ER and mitochondria. Weakening the E-Syt1-PERK interaction or removing the lipid transfer SMP-domain of E-Syt1, compromises mitochondrial respiration. Our findings unravel E-Syt1 as a PERK interacting LTP and molecular component of the lipid trafficking machinery of the EMCS, which critically maintains mitochondrial homeostasis and fitness. [ABSTRACT FROM AUTHOR]