Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis

• DOI: 10.1016/j.celrep.2021.108873
• Publication Date: 2021-03-18T21:18:34Z
• Authors: Irene Anastasia; Nicolò Ilacqua; Andrea Raimondi; Philippe Lemieux; Rana Ghandehari-A...; Guilhem Faure; Sergei L. Mekhedov; Kevin J. Williams; Federico Caicci; Giorgio Valle; Marta Giacomello; Ariel D. Quiroga; Richard Lehner; Michael J. Miksis; Katalin Toth; Thomas Q. de Agui...; Eugene V. Koonin; Luca Scorrano; Luca Pellegrini
• Keywords: Lipid droplet; Organelle; Membrane contact site

Contacts between organelles create microdomains that play major roles in regulating key intracellular activities and signaling pathways, but whether they also regulate systemic functions remains unknown. Here, we report the ultrastructural organization dynamics of inter-organellar contact established by sheets curved rough endoplasmic reticulum closely wrapped around mitochondria (wrappER). To elucidate vivo function this contact, mouse liver fractions enriched wrappER-associated are analyzed transcriptomics, proteomics, lipidomics. The biochemical signature wrappER points to a role biogenesis very-low-density lipoproteins (VLDL). Altering wrappER-mitochondria contacts curtails VLDL secretion increases hepatic fatty acids, lipid droplets, neutral content. Conversely, acute liver-specific ablation Mttp, most upstream regulator biogenesis, recapitulates dyslipidemia phenotype promotes remodeling contact. discovery participate biology suggests an involvement inter-organelle homeostasis.