Lysosomal Expansion Compartments Mediate Zinc and Copper Homeostasis in Caenorhabditis elegans
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Abstract
Zinc is an essential transition metal that participates in many biological processes. In C. elegans , excess zinc is stored in lysosomes in intestinal cells; this process involves increasing the expression of the zinc transporter CDF-2 and remodeling of lysosomes characterized by an increase in the volume of the expansion compartment. To determine if this is a more general property, we investigated other metals. Here we report that lysosomes are remodeled in response to excess copper, manganese, and cadmium, with each metal causing an increase in the volume of the expansion compartment. Mutants with a reduced number of lysosomes were hypersensitive to growth retardation caused by excess copper and manganese, suggesting metal toxicity is prevented by metal sequestration in lysosomes. Using a novel method to analyze isolated lysosomes by X-ray Fluorescence Microscopy we demonstrated that zinc, copper and manganese are detectable in the lumen of lysosomes. To further analyze copper, we examined localization of CUA-1.1, a copper transporter that moves copper into the lumen of lysosomes. Like the zinc transporter CDF-2, CUA-1.1 localizes to both the acidified and expansion compartments in excess copper. These results indicate that the same intestinal lysosomes store zinc, copper and manganese. Lysosome remodeling characterized by an increase in volume of the expansion compartment is not specific to zinc but is a more general phenomenon during metal storage in lysosomes.
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it is unclear if these morphological changes are representative of a “stable” state of a lysosome or if the morphological shifts represent a “transient” stage.
I think this will definitely be an interesting future area of study, and would potentially benefit from examining the expression, localization, and activity of enzymes like superoxide dismutases, which are essential for copper, zinc, and manganese homeostasis.
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Phosphorus, calcium, and iron appeared at the perimeter of the lysosome, whereas sulfur, chlorine, potassium, manganese, copper, and zinc appeared to be distributed throughout the lumen of the lysosome.
This is such a neat technique and the images in figures 3 and 4 are so beautiful!
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does not appear to be acidic
Has this been formally tested? If so, it would be nice to have a citation here.
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In excess manganese, the expansion compartment significantly increased in volume (Figure 1A,E).
The change in CDF-2::GFP intensity is also very striking. Do you think that excess manganese promotes increased transcription and/or translation of cdf-2 mRNA?
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