Reactive oxygen species as signals

Brzezinski, Moe and Ädelroth (2021) point out that ROS names no single chemical entity. It covers molecules or ions formed when O2 is reduced by fewer than four electrons, including superoxide, peroxide and hydroxyl radicals.⁶ They add that these species differ in reactivity, so the term only marks a generally reactive molecule or ion. Superoxide arises from one-electron reduction and is the precursor of other ROS. Its main initial sites in mitochondria are complexes I and III.⁶ Wallace (2013) lists ROS production among the things the energy stored across the mitochondrial inner membrane can modulate, alongside calcium uptake and cellular redox status.¹

Ferramosca and Zara (2014) state that mitochondria of sperm and somatic cells convert 0.2 to 2% of the oxygen they take up into ROS. At low concentrations, they say, these play a physiological role in many cellular processes.² They cite a report that small amounts of hydrogen peroxide stimulate sperm capacitation, hyperactivation and the acrosome reaction. They note that the molecular mechanisms remain largely unknown.³ Kaludercic and Giorgio (2016) describe a balance between formation and removal of ROS and reactive nitrogen species. An imbalance with antioxidant capacity, which they call oxidative or nitrosative stress, can affect lipids, proteins, carbohydrates and DNA.⁴

Kaludercic and Giorgio (2016) argue that ROS and RNS modifications have a dual function. They affect the catalysis of ATP synthase, and so cellular bioenergetics, and they also bear on the permeability transition pore, which they report is formed by ATP synthase dimers.⁵ Rottenberg (2023) describes that pore as a voltage-gated mega-channel. He names excess mitochondrial ROS, through oxidative stress in the matrix, as one physiological activator.⁸ Morse and colleagues (2024) propose that phosphorylations and acetylations of cytochrome c partly inhibit respiration. In their view this keeps an intermediate mitochondrial membrane potential and minimizes ROS.⁹

O'Hara-Wright, Mobini and Gonzalez-Cordero (2022) review hydrogen peroxide and other ROS as ubiquitous signalling molecules. They report defined roles in axial patterning, CNS development, differentiation and regeneration.⁷ They note that NADPH oxidase, which produces H2O2, can be activated by exogenous electrical currents. In amphibian regeneration, H2O2 and Vmem depolarisation overlap in space and time. Studies with NADPH oxidase inhibitors in Xenopus, by Ferreira and colleagues (2016), suggest two-way regulation between redox reactions and electrical fields.⁷ Those authors postulate that a change in membrane potential gives a rapid and dynamic signal for NADPH activation.⁷