Mechanisms of toxicity by and resistance to ferrous iron in anaerobic systems

Iron is an essential element for nearly all life on Earth, primarily for its value as a redox active cofactor. Iron exists predominantly in two biologically relevant redox states: ferric iron, the oxidized state (Fe³⁺), and ferrous iron, the reduced state (Fe²⁺). Fe²⁺ is well known to facilitate electron transfer reactions that can lead to the generation of reactive oxygen species. Less is known about why iron is toxic to cells in the absence of oxygen, yet this phenomenon is critically important for our understanding of life on early Earth and in iron-rich ecosystems today. In this brief review, we will highlight our current understanding of anaerobic Fe²⁺ toxicity, focusing on molecular mechanistic studies in several model systems.