TRANSPORT OF INORGANIC MERCURY AND METHYLMERCURY IN TARGET TISSUES AND ORGANS Original paper

What was reviewed?

This review summarizes how mercury moves through the body by “hitchhiking” on normal nutrient-transport pathways, which helps explain why mercury accumulates in organs such as the intestine, kidney, liver, brain, and placenta. The authors emphasized that mercury rarely circulates as a free ion; instead, it binds tightly to sulfhydryl-containing molecules such as glutathione and cysteine, forming thiol S-conjugates that behave like molecular mimics of endogenous amino acids or peptides and therefore gain access to cells via established membrane transporters.

Who was reviewed?

The paper reviewed mechanistic evidence from toxicology, physiology, and transporter biology rather than a single clinical cohort, integrating animal experiments, cell-based transport models, membrane vesicle studies, and Xenopus oocyte expression systems that isolate specific transport proteins. It also incorporated environmental context by noting that microorganisms in soil and water can methylate inorganic mercury into methylmercury, which then enters food webs and becomes the most common organic mercury form ingested by humans through contaminated fish.

What were the most important findings?

The review identified a unifying transport theme: mercury–thiol complexes cross membranes by exploiting amino acid, peptide, organic anion, and multidrug resistance transport systems, with organ specificity shaped by which transporters dominate each tissue. In the intestine, Hg²⁺ absorption appears limited and ligand-dependent, but the authors proposed that amino acid and peptide transporters can import Hg²⁺ thiol conjugates, while export pathways likely involve multidrug resistance-associated proteins; methylmercury absorbs more efficiently and may enter enterocytes after glutathione catabolism yields cysteine-linked forms that resemble small nutrients. In the kidney, the authors highlighted the proximal tubule as the main accumulation site and described strong evidence that Cys-S-Hg-S-Cys mimics cystine to enter via system b0,+ at the apical membrane, while basolateral uptake of mercuric thiol conjugates relies heavily on organic anion transporters, especially OAT1 and OAT3; they also explained that MRP2 can export chelator–mercury complexes into urine during DMPS or DMSA therapy. For methylmercury, they described molecular mimicry at the blood–brain barrier, where CH₃Hg-S-Cys mimics methionine and uses system L (LAT1/LAT2), and they extended this transporter-centered framework to hepatic canalicular export and placental transfer as clinically important but incompletely defined processes.

What are the greatest implications of this review?

For clinicians, this review clarifies that mercury toxicity depends not only on dose but also on biochemistry and transporter access, which can differ across organs and exposure contexts, making target-organ risk more predictable when you consider thiol binding and transporter expression. For microbiome-informed care, the key translational point is that the microbiome can set exposure form upstream by converting inorganic mercury to methylmercury in environmental reservoirs, while host gut and renal handling then determines systemic delivery and retention; this supports pairing exposure assessment with mechanistic biomarkers that reflect thiol status and transporter-relevant physiology rather than assuming uniform tissue uptake. The review also strengthens the rationale for chelation strategies that deliberately form transportable mercury complexes and leverage renal export systems such as MRP2, while underscoring that gaps remain in fully mapping intestinal, hepatic sinusoidal, and placental transport pathways that likely influence interindividual susceptibility.