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X-Ray Fluorescence Microscopy Reveals Accumulation and Secretion of Discrete Intracellular Zinc Pools in the Lactating Mouse Mammary Gland

Journal Article · · PLoS ONE
 [1];  [2];  [3];  [3];  [2]
  1. Pennsylvania State Univ., University Park, PA (United States). Dept. of Nutritional Sciences; DOE/OSTI
  2. Pennsylvania State Univ., University Park, PA (United States). Dept. of Nutritional Sciences
  3. Argonne National Lab. (ANL), Argonne, IL (United States)
+ Show Author Affiliations
Background: The mammary gland is responsible for the transfer of a tremendous amount of zinc (,1–3 mg zinc/day) from maternal circulation into milk during lactation to support the growth and development of the offspring. When this process is compromised, severe zinc deficiency compromises neuronal development and immune function and increases infant morbidity and/or mortality. It remains unclear as to how the lactating mammary gland dynamically integrates zinc import from maternal circulation with the enormous amount of zinc that is secreted into milk. Methodology/Principal Findings: Herein we utilized X-ray fluorescence microscopy (XFM) which allowed for the visualization and quantification of the process of zinc transfer through the mammary gland of the lactating mouse. Our data illustrate that a large amount of zinc first accumulates in the mammary gland during lactation. Interestingly, this zinc is not cytosolic, but accumulated in large, discrete sub-cellular compartments. These zinc pools were then redistributed to small intracellular vesicles destined for secretion in a prolactin-responsive manner. Confocal microscopy identified mitochondria and the Golgi apparatus as the sub-cellular compartments which accumulate zinc; however, zinc pools in the Golgi apparatus, but not mitochondria are redistributed to vesicles destined for secretion during lactation. Conclusions/Significance: Our data directly implicate the Golgi apparatus in providing a large, mobilizable zinc storage pool to assist in providing for the tremendous amount of zinc that is secreted into milk. Interestingly, our study also provides compelling evidence that mitochondrial zinc pools expand in the mammary gland during lactation which we speculate may play a role in regulating mammary gland function.
Research Organization:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1627411
Journal Information:
PLoS ONE, Journal Name: PLoS ONE Journal Issue: 6 Vol. 5; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (16)

Milk-derived miRNA profiles elucidate molecular pathways that underlie breast dysfunction in women with common genetic variants in SLC30A2 journal September 2019
Subtype-specific accumulation of intracellular zinc pools is associated with the malignant phenotype in breast cancer journal January 2016
Demand for Zn2+ in Acid-Secreting Gastric Mucosa and Its Requirement for Intracellular Ca2+ journal June 2011
The Zinc Sensing Receptor, ZnR/GPR39, in Health and Disease journal February 2018
Zinc regulates ERp44-dependent protein quality control in the early secretory pathway journal February 2019
A genetic variant in SLC30A2 causes breast dysfunction during lactation by inducing ER stress, oxidative stress and epithelial barrier defects journal February 2018
Superiority of SpiroZin2 Versus FluoZin-3 for monitoring vesicular Zn2+ allows tracking of lysosomal Zn2+ pools journal October 2018
Subcellular redistribution and mitotic inheritance of transition metals in proliferating mouse fibroblast cells journal January 2013
Remodeling of Zn 2+ homeostasis upon differentiation of mammary epithelial cells journal January 2020
Zinc-dependent lysosomal enlargement in TRPML1-deficient cells involves MTF-1 transcription factor and ZnT4 (Slc30a4) transporter journal March 2013
Essential Role for Zinc Transporter 2 (ZnT2)-mediated Zinc Transport in Mammary Gland Development and Function during Lactation journal May 2015
Lysosome-related Organelles as Mediators of Metal Homeostasis journal August 2014
ZnT4 provides zinc to zinc-dependent proteins in the trans -Golgi network critical for cell function and Zn export in mammary epithelial cells journal August 2012
Compound Heterozygous Mutations in SLC30A2/ZnT2 Results in Low Milk Zinc Concentrations: A Novel Mechanism for Zinc Deficiency in a Breast-Fed Infant journal May 2013
The zinc sensing receptor ZnR GPR39 in health and disease journal January 2017
Zinc in Specialized Secretory Tissues: Roles in the Pancreas, Prostate, and Mammary Gland journal March 2011

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