Mechanisms of Co, Ni, and Mn toxicity: From exposure and homeostasis to their interactions with and impact on lipids and biomembranes.

Anthropogenic activity has increased human exposure to metals and resulted in metal induced toxicity. Essential trace elements like cobalt (Co), nickel (Ni), and manganese (Mn) are best known for their roles as important cofactors in many enzymes involved in signalling, metabolism, and response to oxidative stress. However, deficiencies as well as long-term overexposure to these metals can result in negative health effects. Co has been associated with cardiomyopathy, lung disease, and hearing damage, while Ni is a known carcinogen, as well as a common sensitizing metal. Mn is best classified as a neurotoxicant that causes a disorder alike to idiopathic Parkinson's disease known as Manganism. Although the mechanisms of Co, Ni, and Mn toxicity are complex and have yet to be fully elucidated, research over the years has provided useful insights into understanding metal-induced detrimental effects at the cellular and molecular level. One area of research that has been explored in less detail are metal interactions with lipids and biological membranes, which are a potentially critical target as membranes are the first point of contact for cells. This review covers the current understandings of Co, Ni and Mn toxicity, in terms of human exposure, homeostasis and mechanisms of transport, potential cellular targets, and, of primary focus, metal interactions with lipid and biomembranes. A variety of effects like membrane rigidification, leakage affecting membrane potentials, lipid phase changes, alterations in lipid metabolism and changes of cellular morphology illustrate the vast potential for metal-based membrane effects contributing to their toxicity.