ArticleScientific reports2015
ZnT2 is a critical mediator of lysosomal-mediated cell death during early mammary gland involution.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- Mammary adipocyte plasticity and epithelial crosstalk: roles in development, remodeling, and disease.Reviews in endocrine & metabolic disorders · 2026Review
- Zinc dyshomeostasis, mitochondrial dysfunction, and their pathological cycle in ischemic stroke pathophysiology: Mechanisms and potential therapeutic targets.Redox biology · 2026Review
- From Embryogenesis to Senescence: The Role of Mammary Gland Physiology in Breast Cancer Risk.Cancers · 2025Review
- On the genesis and unique functions of zinc neuromodulation.Journal of neurophysiology · 2024Review
- Emerging Perspectives in Zinc Transporter Research in Prostate Cancer: An Updated Review.Nutrients · 2024Review
- Lysosome-related organelles contain an expansion compartment that mediates delivery of zinc transporters to promote homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- miR-30a-3p Regulates Autophagy in the Involution of Mice Mammary Glands.International journal of molecular sciences · 2023Article
- Breast cancers co-opt normal mechanisms of tolerance to promote immune evasion and metastasis.American journal of physiology. Cell physiology · 2022Review
- Zinc Signaling in the Mammary Gland: For Better and for Worse.Biomedicines · 2021Review
- The molecular basis of mammary gland development and epithelial differentiation.Seminars in cell & developmental biology · 2021Review
- Estrogen exacerbates mammary involution through neutrophil-dependent and -independent mechanism.eLife · 2020Article
- ZnT2 is an electroneutral proton-coupled vesicular antiporter displaying an apparent stoichiometry of two protons per zinc ion.PLoS computational biology · 2019Article
- High proportion of transient neonatal zinc deficiency causing alleles in the general population.Journal of cellular and molecular medicine · 2019Article
- Superiority of SpiroZin2 Versus FluoZin-3 for monitoring vesicular ZnScientific reports · 2018Article
- ZnT2 is critical for lysosome acidification and biogenesis during mammary gland involution.American journal of physiology. Regulatory, integrative and comparative physiology · 2018Article
- A genetic variant in SLC30A2 causes breast dysfunction during lactation by inducing ER stress, oxidative stress and epithelial barrier defects.Scientific reports · 2018Article
- Expression of the mRNA stability regulator Tristetraprolin is required for lactation maintenance in the mouse mammary gland.Oncotarget · 2018Article
- Zinc transporter 2 interacts with vacuolar ATPase and is required for polarization, vesicle acidification, and secretion in mammary epithelial cells.The Journal of biological chemistry · 2017Article
- Zinc Signals and Immunity.International journal of molecular sciences · 2017Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Mammary gland involution is the most dramatic example of physiological cell death. It occurs through an initial phase of lysosomal-mediated cell death (LCD) followed by mitochondrial-mediated apoptosis. Zinc (Zn) activates both LCD and apoptosis in vitro. The Zn transporter ZnT2 imports Zn into vesicles and mitochondria and ZnT2-overexpression activates cell death in mammary epithelial cells (MECs). We tested the hypothesis that ZnT2-mediated Zn transport is critical for mammary gland involution in mice. Following weaning, ZnT2 abundance increased in lysosomes and mitochondria, which paralleled Zn accumulation in each of these organelles. Adenoviral expression of ZnT2 in lactating mouse mammary glands in vivo increased Zn in lysosomes and mitochondria and activated LCD and apoptosis, promoting a profound reduction in MECs and alveoli. Injection of TNFα, a potent activator of early involution, into the mammary gland fat pads of lactating mice increased ZnT2 and Zn in lysosomes and activated premature involution. Exposure of cultured MECs to TNFα redistributed ZnT2 to lysosomes and increased lysosomal Zn, which activated lysosomal swelling, cathepsin B release, and LCD. Our data implicate ZnT2 as a critical mediator of cell death during involution and importantly, that as an initial involution signal, TNFα redistributes ZnT2 to lysosomes to activate LCD.
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