Bassot 2023 Cell Rep

Bassot A, Chen J, Takahashi-Yamashiro K, Yap MC, Gibhardt CS, Le GNT, Hario S, Nasu Y, Moore J, Gutiérrez T, Mina L, Mast H, Moses A, Bhat R, Ballanyi K, Lemieux H, Sitia R, Zito E, Bogeski I, Campbell RE, Simmen T (2023) The endoplasmic reticulum kinase PERK interacts with the oxidoreductase ERO1 to metabolically adapt mitochondria. Cell Rep 42:111899. https://doi.org/10.1016/j.celrep.2022.111899

» PMID: 36586409 Open Access

Bassot Arthur, Chen Junsheng, Takahashi-Yamashiro Kei, Yap Megan C, Gibhardt Christine Silvia, Le Giang NT, Hario Saaya, Nasu Yusuke, Moore Jack, Gutierrez Tomas, Mina Lucas, Mast Heather, Moses Audric, Bhat Rakesh, Ballanyi Klaus, Lemieux Helene, Sitia Roberto, Zito Ester, Bogeski Ivan, Campbell Robert E, Simmen Thomas (2023) Cell Rep

Abstract: Endoplasmic reticulum (ER) homeostasis requires molecular regulators that tailor mitochondrial bioenergetics to the needs of protein folding. For instance, calnexin maintains mitochondria metabolism and mitochondria-ER contacts (MERCs) through reactive oxygen species (ROS) from NADPH oxidase 4 (NOX4). However, induction of ER stress requires a quick molecular rewiring of mitochondria to adapt to new energy needs. This machinery is not characterized. We now show that the oxidoreductase ERO1⍺ covalently interacts with protein kinase RNA-like ER kinase (PERK) upon treatment with tunicamycin. The PERK-ERO1⍺ interaction requires the C-terminal active site of ERO1⍺ and cysteine 216 of PERK. Moreover, we show that the PERK-ERO1⍺ complex promotes oxidization of MERC proteins and controls mitochondrial dynamics. Using proteinaceous probes, we determined that these functions improve ER-mitochondria Ca²⁺ flux to maintain bioenergetics in both organelles, while limiting oxidative stress. Therefore, the PERK-ERO1⍺ complex is a key molecular machinery that allows quick metabolic adaptation to ER stress. • Keywords: CP: Metabolism, CP: Molecular biology, ER, ER stress, ERO1, MAMs, MERCs, PERK, Bioenergetics, Endoplasmic reticulum, Mitochondria, Mitochondria-associated membranes, Mitochondria-endoplasmic reticulum contacts, Oxidoreductase • Bioblast editor: Plangger M • O2k-Network Lab: CA Edmonton Lemieux H

Labels: MiParea: Respiration 

Organism: Human, Mouse  Tissue;cell: HEK, Fibroblast  Preparation: Intact cells 

Coupling state: LEAK, ROUTINE, ET  Pathway: ROX  HRR: Oxygraph-2k 

2024-03