From the Cosmos to the Cell: The Central Role of Iron in the Chemistry and Evolution of Life.

Iron, with the unique stability of its nucleus, occupies an unusual position among the elements: its abundance on Earth is not simply a geological accident but a direct consequence of nuclear reactions that happened inside stars billions of years ago. Formed at the final stages of fusion in stars, iron spread through space by supernova explosions and became part of the material that formed Earth, eventually becoming the dominant component of the planet's core. At the surface, iron's redox chemistry shaped the early atmosphere and oceans, and its availability as a soluble ferrous ion in the anaerobic Archean ocean made it a natural cofactor for the first enzymatic reactions. That same redox flexibility and the ability of iron to shuttle between Fe2+ and Fe3+ across a wide range of electrochemical potentials explain why virtually every major metabolic pathway in biology depends on iron in one form or another. Yet iron is also dangerous: free and chelated iron can catalyze the production of toxic hydroxyl radicals through Fenton chemistry, the reactivity of which depends strongly on the nature of the chelating ligand, and every living system must balance its need for iron against the oxidative damage that uncontrolled iron causes. This tension between catalytic necessity and chemical toxicity has driven much of the regulatory complexity we observe in modern iron metabolism. In this review, we first outline iron's journey from its formation in stars to its role in shaping Earth's structure and the emergence of early iron-dependent biology. We then discuss in detail how fundamental physical and chemical factors continue to influence living systems.