Zinc Homeostasis and Human Health

Zinc is an indispensable micronutrient that underpins a vast array of physiological processes, ranging from enzymatic catalysis and gene expression to immune competence and cellular signalling. In humans, systemic zinc homeostasis is governed by coordinated intestinal absorption, plasma transport bound to albumin and metallothioneins, and renal excretion. At the cellular level, two transporter families—ZIP (Zrt- and Irt-like proteins) and ZnT (zinc transporters)—mediate zinc influx and efflux respectively, while metallothioneins buffer intracellular Zn2+ concentrations. Tight regulation ensures that zinc-dependent enzymes and transcription factors function optimally, supporting growth, neurodevelopment and antioxidant defence. Conversely, zinc deficiency can lead to growth retardation, impaired immune responses and metabolic disturbances, whereas excess zinc may disrupt copper uptake and provoke toxicity. Globally, zinc deficiency remains a significant public-health challenge, driving efforts to refine supplementation strategies and to elucidate molecular targets for therapeutic intervention in disorders ranging from malnutrition to cancer.

Research from Nature Portfolio

Recent studies have elucidated the structural basis of autoregulation in ZIP-family transporters. High-resolution cryo-electron microscopy revealed a homodimeric transporter conformation in which a cytoplasmic loop bearing conserved histidines senses intracellular Zn2+ and modulates channel opening. Biochemical assays demonstrated that this built-in sensor attenuates zinc uptake when cytosolic levels rise, providing a mechanistic framework for feedback control of cellular zinc influx.

Zinc Homeostasis and Human Health publication trend

The graph below shows the total number of articles in zinc homeostasis and human health across all publications each year (not limited to Nature Index journals).

Technical terms

Homeostasis: Maintenance of stable internal zinc concentrations across tissues and cells.

ZIP transporters: Membrane proteins that import Zn2+ into the cytosol from extracellular or organellar stores.

ZnT transporters: Membrane proteins that export Zn2+ from the cytosol or sequester it into organelles.

Metallothioneins: Small, cysteine-rich proteins that bind and store zinc, buffering intracellular levels.

Zn2+: The divalent ionic form of zinc that participates in enzymatic, structural and signalling roles.

References

1. Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets. Signal Transduction and Targeted Therapy (2024).
2. Structural mechanism of intracellular autoregulation of zinc uptake in ZIP transporters. Nature Communications (2023).
3. Zinc as a Gatekeeper of Immune Function. Nutrients (2017).
4. The biological inorganic chemistry of zinc ions. Archives of Biochemistry and Biophysics (2016).