%0 Journal Article
%T The endoplasmic reticulum kinase PERK interacts with the oxidoreductase ERO1 to metabolically adapt mitochondria.
%A Bassot A
%A Chen J
%A Takahashi-Yamashiro K
%A Yap MC
%A Gibhardt CS
%A Le GNT
%A Hario S
%A Nasu Y
%A Moore J
%A Gutiérrez T
%A Mina L
%A Mast H
%A Moses A
%A Bhat R
%A Ballanyi K
%A Lemieux H
%A Sitia R
%A Zito E
%A Bogeski I
%A Campbell RE
%A Simmen T
%J Cell Rep
%V 42
%N 1
%D 01 2023 31
%M 36586409
暂无%R 10.1016/j.celrep.2022.111899
%X 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.