A Window to the Potassium World. The Evidence of Potassium Energetics in the Mitochondria and Identity of the Mitochondrial ATP-Dependent K+ Channel

The conclusions made in the three papers published in Function by Juhaszova et al. [Function, 3, 2022, zqab065, zqac001, zqac018], can be seen as a breakthrough in bioenergetics and mitochondrial medicine. For more than half a century, it has been believed that mitochondrial energetics is solely protonic and is based on the generation of electrochemical potential of hydrogen ions across the inner mitochondrial membrane upon oxidation of respiratory substrates, resulting in the generation of ATP via reverse transport of protons through the ATP synthase complex. Juhaszova et al. demonstrated that ATP synthase transfers not only protons, but also potassium ions, with the generation of ATP. This mechanism seems logical, given the fact that in eukaryotic cells, the concentration of potassium ions is several million times higher than the concentration of protons. The transport of K+ through the ATP synthase was enhanced by the activators of mitochondrial ATP-dependent K+ channel (K-m/ATP), leading to the conclusion that ATP synthase is the material essence of K-m/ATP. Beside ATP generation, the transport of osmotically active K+ to the mitochondrial matrix is accompanied by water entry to the matrix, leading to an increase in the matrix volume and activation of mitochondrial respiration with the corresponding increase in the ATP synthesis, which suggests an advantage of such transport for energy production. The driving force for K+ transport into the mitochondria is the membrane potential; an excess of K+ is exported from the matrix by the hypothetical K+/H+ exchangers. Inhibitory factor 1 (IF1) plays an important role in the activation of K-m/ATP by increasing the chemo-mechanical efficiency of ATP synthase, which may be a positive factor in the protective anti-ischemic signaling.

Automated summary

The conclusions made by Juhaszova et al. in their three papers published in Function are considered a breakthrough in bioenergetics and mitochondrial medicine. They discovered that ATP synthase not only transports protons, but also potassium ions, leading to the generation of ATP. This potassium ion transport not only contributes to energy production, but may also play a positive role in protective anti-ischemic signaling.