Modulation of methylmercury uptake by methionine: Prevention of mitochondrial dysfunction in rat liver slices by a mimicry mechanism Original paper

What was studied?

This study tested whether methionine can reduce mercury uptake and prevent mitochondrial injury in liver tissue by interfering with the “molecular mimicry” route used by the methylmercury–cysteine complex (MeHg–Cys). Using rat liver slices, the authors compared exposure to MeHg alone versus MeHg–Cys, then measured mercury accumulation in whole slices and isolated mitochondria, along with reactive species formation, oxygen consumption, and cell viability. They also evaluated whether a short methionine pre-treatment changes these outcomes, focusing on the liver because it can accumulate substantial mercury after MeHg exposure.

Who was studied?

The investigators studied adult male Wistar rats as the tissue source and performed an ex vivo liver-slice experiment rather than a human study. They prepared 300 μm liver slices and assigned them to treatment conditions that included MeHg (25 μM), cysteine, MeHg–Cys (25 μM each), methionine (250 μM), and methionine pre-treatment before MeHg or MeHg–Cys exposure. The exposures occurred for 30 minutes at 37 °C, and the team then isolated mitochondria from the slices to quantify mitochondrial-specific effects alongside whole-tissue measures.

What were the most important findings?

MeHg increased mercury levels in liver slices and in mitochondria, and the MeHg–Cys complex produced higher mercury uptake than MeHg alone, indicating that the cysteine complex enhances cellular entry and mitochondrial delivery. The MeHg–Cys condition also produced stronger mitochondrial oxidative stress signals, with higher reactive species formation in mitochondria than the MeHg-alone condition, and MeHg reduced oxygen consumption in slices, with a more pronounced effect when mercury was presented as MeHg–Cys. Methionine pre-treatment decreased MeHg uptake by liver slices and prevented the downstream toxicity pattern, preserving mitochondrial function and cell viability in both MeHg and MeHg–Cys conditions. In microbiome-signature terms, the key association is functional: MeHg presented as a cysteine conjugate behaves like a transportable nutrient mimic and drives mitochondrial stress in hepatic tissue, while methionine counters this by reducing uptake and limiting mitochondrial injury.

What are the greatest implications of this study?

For clinicians, this paper supports a clear mechanism for why exposure form matters: MeHg–Cys increases hepatic and mitochondrial mercury burden and amplifies mitochondrial oxidative stress, which likely drives early energy failure and cell injury in the liver. It also shows that methionine can meaningfully blunt uptake and toxicity in a controlled tissue model, positioning amino-acid competition or binding interactions as a plausible supportive strategy during acute exposures, even though the authors note that in vivo dynamics could differ by timing and distribution. For microbiome-informed risk framing, the practical takeaway is that methylmercury behaves as a conjugate that uses nutrient-like entry routes, so upstream factors that influence conjugate availability can shift organ burden and mitochondrial stress signals that later appear as systemic toxicity.