RRC ID 80837
Author Essig YJ, Leszczyszyn OI, Almutairi N, Harrison-Smith A, Blease A, Zeitoun-Ghandour S, Webb SM, Blindauer CA, Stürzenbaum SR.
Title Juggling cadmium detoxification and zinc homeostasis: A division of labour between the two C. elegans metallothioneins.
Journal Chemosphere
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 His3Cys 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.
Volume 350
Pages 141021
Published 2024-2-1
DOI 10.1016/j.chemosphere.2023.141021
PII S0045-6535(23)03291-5
PMID 38151062
PMC PMC11134313
MeSH Animals Cadmium* / toxicity Caenorhabditis elegans* / metabolism Metallothionein / metabolism Metals / metabolism Protein Isoforms / genetics Protein Isoforms / metabolism Zinc / metabolism
C.elegans tm1770 tm1700