Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Sep;1797(9):1672-80.
doi: 10.1016/j.bbabio.2010.06.005. Epub 2010 Jun 22.

Mitochondrial respiration and membrane potential are regulated by the allosteric ATP-inhibition of cytochrome c oxidase

Rabia Ramzan  1 , Katrin Staniek, Bernhard Kadenbach, Sebastian Vogt
Affiliations
Free article

Mitochondrial respiration and membrane potential are regulated by the allosteric ATP-inhibition of cytochrome c oxidase

Rabia Ramzan et al. Biochim Biophys Acta. 2010 Sep.
Free article

Abstract

This paper describes the problems of measuring the allosteric ATP-inhibition of cytochrome c oxidase (CcO) in isolated mitochondria. Only by using the ATP-regenerating system phosphoenolpyruvate and pyruvate kinase full ATP-inhibition of CcO could be demonstrated by kinetic measurements. The mechanism was proposed to keep the mitochondrial membrane potential (DeltaPsi(m)) in living cells and tissues at low values (100-140 mV), when the matrix ATP/ADP ratios are high. In contrast, high DeltaPsi(m) values (180-220 mV) are generally measured in isolated mitochondria. By using a tetraphenyl phosphonium electrode we observed in isolated rat liver mitochondria with glutamate plus malate as substrates a reversible decrease of DeltaPsi(m) from 233 to 123 mV after addition of phosphoenolpyruvate and pyruvate kinase. The decrease of DeltaPsi(m) is explained by reversal of the gluconeogenetic enzymes pyruvate carboxylase and phosphoenolpyruvate carboxykinase yielding ATP and GTP, thus increasing the matrix ATP/ADP ratio. With rat heart mitochondria, which lack these enzymes, no decrease of DeltaPsi(m) was found. From the data we conclude that high matrix ATP/ADP ratios keep DeltaPsi(m) at low values by the allosteric ATP-inhibition of CcO, thus preventing the generation of reactive oxygen species which could generate degenerative diseases. It is proposed that respiration in living eukaryotic organisms is normally controlled by the DeltaPsi(m)-independent "allosteric ATP-inhibition of CcO." Only when the allosteric ATP-inhibition is switched off under stress, respiration is regulated by "respiratory control," based on DeltaPsi(m) according to the Mitchell Theory.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

Substances

LinkOut - more resources