Mitochondrial oxidant leak
Mitochondrial reactive oxygen species↓
Also searched as Mitochondrial reactive oxygen species.
Electrons escaping the energy-production chain and reacting with oxygen before they should. A small amount is the signal that tells the cell to build more mitochondria; a constant leak is damage to the very machinery producing it.
In depth
Electrons escaping the energy-production chain and reacting with oxygen before they should — a constant leak damages mitochondrial DNA and the machinery producing it.
What drives it
Mitochondrial energy reduces it.
Dysfunctional respiratory complexes leak electrons, increasing mitochondrial reactive oxygen species production. doi 10.1016/j.cell.2022.11.001 · PMID 23746838 · PMC7139312
Heat instead of storage reduces it.
CONTESTED, and the map marks it so. The modeling source states the effect at complex III only: 'A mild uncoupling in State 4 can markedly decrease the superoxide generation' (PMID 9746310 - Demin, Kholodenko & Skulachev, A model of O2- generation in the complex III of the electron transport chain, Mol Cell Biochem 1998;184:21-33; doi 10.1023/A:1006849920918). That is a model, in State 4, at a membrane potential above the range found in respiring mitochondria, and it does not address complex I. The opposing stream is explicit: 'Thus present evidence does not support mild uncoupling as a physiologically relevant alleviator of oxidative damage' (PMID 21936806 - Shabalina & Nedergaard, Mitochondrial ('mild') uncoupling and ROS production: physiologically relevant or not?, Biochem Soc Trans 2011;39:1305-1309; doi 10.1042/BST0391305). Both are shown because the question is not settled. doi 10.1023/A:1006849920918 · PMID 9746310
What it drives
It increases Mitochondrial pore.
10.1038/s41418-023-01187-0 — Oxidative stress and a calcium overload together prise open the pore: cyclophilin D moves to the inner membrane under high matrix calcium, and the channel opens. doi 10.1038/s41418-023-01187-0
It reduces Mitochondrial DNA.
mtDNA lies adjacent to the inner membrane and is damaged by locally generated ROS. doi 10.1016/j.cell.2022.11.001 · PMID 23746838 · PMC7139312
It increases Antioxidant defense.
Mitochondrial ROS act as a signal that activates Nrf2-dependent antioxidant transcription — the hormetic arm. doi 10.1016/j.cell.2022.11.001 · PMID 23746838 · PMC7139312
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.