Abstract:
:Zinc is an essential trace element, and impaired zinc homeostasis is implicated in the pathogenesis of various human diseases. However, the mechanisms cells use to respond to zinc deficiency are poorly understood. We previously reported that amyotrophic lateral sclerosis (ALS)-linked pathogenic mutants of SOD1 cause chronic endoplasmic reticulum (ER) stress through specific interactions with Derlin-1, which is a component of the ER-associated degradation machinery. Moreover, we recently demonstrated that this interaction is common to ALS-linked SOD1 mutants, and wild-type SOD1 (SOD1(WT)) comprises a masked Derlin-1 binding region (DBR). Here, we found that, under zinc-deficient conditions, SOD1(WT) adopts a mutant-like conformation that exposes the DBR and induces the homeostatic ER stress response, including the inhibition of protein synthesis and induction of a zinc transporter. We conclude that SOD1 has a function as a molecular switch that activates the ER stress response, which plays an important role in cellular homeostasis under zinc-deficient conditions.
journal_name
Mol Celljournal_title
Molecular cellauthors
Homma K,Fujisawa T,Tsuburaya N,Yamaguchi N,Kadowaki H,Takeda K,Nishitoh H,Matsuzawa A,Naguro I,Ichijo Hdoi
10.1016/j.molcel.2013.08.038subject
Has Abstractpub_date
2013-10-10 00:00:00pages
75-86issue
1eissn
1097-2765issn
1097-4164pii
S1097-2765(13)00638-2journal_volume
52pub_type
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