Juggling Cadmium Detoxification and Zinc Homeostasis: A Division of Labour Between the Two C. Elegans Metallothioneins

Overview

Journal Chemosphere

Specialties Biology
Chemistry
Environmental Health

Date 2023 Dec 27

PMID 38151062

Authors

Yona J Essig

Oksana I Leszczyszyn

Norah Almutairi

Alexandra Harrison-Smith

Alix Blease

Sukaina Zeitoun-Ghandour

Sam M Webb

Claudia A Blindauer

Stephen R Sturzenbaum

Affiliations

Soon will be listed here.

Abstract

The chemical properties of toxic cadmium and essential zinc are very similar, and organisms require intricate mechanisms that drive selective handling of metals. Previously regarded as unspecific "metal sponges", metallothioneins (MTLs) are emerging as metal selectivity filters. By utilizing C. elegans mtl-1 and mtl-2 knockout strains, metal accumulation in single worms, single copy fluorescent-tagged transgenes, isoform specific qPCR and lifespan studies it was possible to demonstrate that the handling of cadmium and zinc by the two C. elegans metallothioneins differs fundamentally: the MTL-2 protein can handle both zinc and cadmium, but when it becomes unavailable, either via a knockout or by elevated cadmium exposure, MTL-1 takes over zinc handling, leaving MTL-2 to sequester cadmium. This division of labour is reflected in the folding behaviour of the proteins: MTL-1 folded well in presence of zinc but not cadmium, the reverse was the case for MTL-2. These differences are in part mediated by a zinc-specific mononuclear HisCys site in the C-terminal insertion of MTL-1; its removal affected the entire C-terminal domain and may shift its metal selectivity towards zinc. Overall, we uncover how metallothionein isoform-specific responses and protein properties allow C. elegans to differentiate between toxic cadmium and essential zinc.

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