Why Dysbiosis, SIBO, Hydrogen Sulfide Intolerance, MCAS, and Long COVID May All Be Downstream of a Single Event — Peroxynitrite and the iron-sulfur cluster catastrophe: how the engine actually breaks

So far I've said the colonocyte's mitochondria "start to fail." That's a placeholder. Let's open it up, because the specific way they fail is what ties the gut to inflammation, infection, mast cells, and long COVID. In chronic inflammation, a gene called NOS2 — encoding inducible nitric oxide synthase (iNOS) — gets switched on hard, flooding the tissue with nitric oxide (NO). At the same time, damaged mitochondria and inflammatory enzymes called NADPH oxidases (NOX) spill out superoxide, a reactive oxygen molecule. Nitric oxide and superoxide find each other and react almost instantly to form peroxynitrite (ONOO⁻) — one of the most destructive reactive nitrogen species in all of biology. Peroxynitrite is not a vague "oxidative stress." It is a precision-guided wrecking ball, and it has a favorite target. That target is the iron-sulfur cluster. Iron-sulfur clusters are tiny scaffolds — built from iron atoms and inorganic sulfur, in arrangements like 2Fe-2S and 4Fe-4S — that sit at the catalytic heart of many of the most important enzymes in your mitochondria. Think of them as the spark plugs of cellular respiration: small, easily fouled, and absolutely essential. Peroxynitrite oxidizes and tears these clusters apart. Look at what depends on them: Aconitase, a TCA-cycle enzyme, carries a 4Fe-4S cluster — damage it and the central metabolic wheel seizes. Complex I of the electron