Biopolym. Cell. 2019; 35(3):195-196.
Chronicle and Information
The cell nucleus as sensor of environmental pollution: Amyloid, neurodegeneration and aging
- IUF-Leibniz Research Institute of Environmental Medicine at Heinrich-Heine-University Duesseldorf
Duesseldorf, Germany - Washington University
St. Louis, USA
Abstract
Two major environmental challenges are predominant - climate change and the biodiversity
crisis. Also, pollutants are distributed globally.
We identified the cell nucleus as a sensitive
sensor for bio-effects of pollutants such as mercury and nanoparticles. Our investigations focus
on the role of pollutant-induced nuclear amyloid
formation in neural signaling, neurotoxicity and
accelerated aging in the nematode Caenorhabditis
elegans. Methods: At present, the majority of
investigations on the toxicology of pollutants
address short-term effects. While this approach
allows for the identification of uptake pathways,
exposition and acute toxicity, xenobiotic-organism interactions that manifest later in an adult
life are missed. To characterize effects of pollutants over the entire life span, all analyses are
performed in the nematode C. elegans. Results:
We show that mercury and nano silica effect
widespread protein aggregation. Proteomic profiling revealed that both pollutants promote
segregation of proteins belonging to the gene
ontology (GO) group of ‘protein folding, proteolysis and stress response’ to an SDS-resistant
aggregome network. Candidate proteins in this group include chaperones, heat shock proteins
and subunits of the 26S proteasome which are
all decisively involved in protein homeostasis.
Another emerging GO group is translation.
Crucial proteins such as the methyltransferase
fibrillarin aggregate, segregate and thus reduce
translational activity. The metabolic changes
contribute to neurodegeneration and starvation
which in turn manifests in petite worms showing motoric and olfactory deficits. Conclusions:
A picture emerges that pollutants induce premature aging, thereby reducing the health span
and longevity of C. elegans. The neural system
of the worm represents a prominent target organ
showing neuromuscular defects that among
others manifest in neurodegeneration of single
neurons in combination with altered locomotion, reduced fecundity and impaired olfaction.
As C. elegans leads a dual life, e.g. in the lab
and in ecosystems, our results explain how
environmental pollutants reduce the fitness of
wild worms. Concerning the survival of wild
populations the flexibility of adaptive gene expression and proteomes likely determines biodiversity, namely resilience against pollutantand climate-stress.
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