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Proteotoxic stress and ageing triggers the loss of redox homeostasis across cellular compartments
Author(s) -
Kirstein Janine,
Morito Daisuke,
Kakihana Taichi,
Sugihara Munechika,
Minnen Anita,
Hipp Mark S,
NussbaumKrammer Carmen,
Kasturi Prasad,
Hartl F Ulrich,
Nagata Kazuhiro,
Morimoto Richard I
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201591711
Subject(s) - proteostasis , biology , caenorhabditis elegans , microbiology and biotechnology , endoplasmic reticulum , cytosol , cellular compartment , organelle , protein folding , redox , unfolded protein response , homeostasis , autophagy , biochemistry , cell , chemistry , apoptosis , organic chemistry , gene , enzyme
The cellular proteostasis network integrates the protein folding and clearance machineries in multiple sub‐cellular compartments of the eukaryotic cell. The endoplasmic reticulum ( ER ) is the site of synthesis and folding of membrane and secretory proteins. A distinctive feature of the ER is its tightly controlled redox homeostasis necessary for the formation of inter‐ and intra‐molecular disulphide bonds. Employing genetically encoded in vivo sensors reporting on the redox state in an organelle‐specific manner, we show in the nematode Caenorhabditis elegans that the redox state of the ER is subject to profound changes during worm lifetime. In young animals, the ER is oxidizing and this shifts towards reducing conditions during ageing, whereas in the cytosol the redox state becomes more oxidizing with age. Likewise, the redox state in the cytosol and the ER change in an opposing manner in response to proteotoxic challenges in C. elegans and in HeLa cells revealing conservation of redox homeostasis. Moreover, we show that organelle redox homeostasis is regulated across tissues within C. elegans providing a new measure for organismal fitness.