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The Dual Function of Reactive Oxygen/Nitrogen Species in Bioenergetics and Cell Death: The Role of ATP Synthase.

ABSTRACT: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) targeting mitochondria are major causative factors in disease pathogenesis. The mitochondrial permeability transition pore (PTP) is a mega-channel modulated by calcium and ROS/RNS modifications and it has been described to play a crucial role in many pathophysiological events since prolonged channel opening causes cell death. The recent identification that dimers of ATP synthase form the PTP and the fact that posttranslational modifications caused by ROS/RNS also affect cellular bioenergetics through the modulation of ATP synthase catalysis reveal a dual function of these modifications in the cells. Here, we describe mitochondria as a major site of production and as a target of ROS/RNS and discuss the pathophysiological conditions in which oxidative and nitrosative modifications modulate the catalytic and pore-forming activities of ATP synthase.

SUBMITTER: Kaludercic N

PROVIDER: S-EPMC4806282 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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The Dual Function of Reactive Oxygen/Nitrogen Species in Bioenergetics and Cell Death: The Role of ATP Synthase.

Kaludercic Nina N Giorgio Valentina V

Oxidative medicine and cellular longevity 20160310

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) targeting mitochondria are major causative factors in disease pathogenesis. The mitochondrial permeability transition pore (PTP) is a mega-channel modulated by calcium and ROS/RNS modifications and it has been described to play a crucial role in many pathophysiological events since prolonged channel opening causes cell death. The recent identification that dimers of ATP synthase form the PTP and the fact that posttranslational mod ...[more]

PMID: 27034734

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Project description:In this study, the ATP synthase of Ignicoccus hospitalis was purified, characterized, and structurally compared to the respective enzymes of the other Ignicoccus species, to shed light on energy conservation in this unique group of archaea. The crenarchaeal genus Ignicoccus comprises three described species, i.e., I. hospitalis and Ignicoccus islandicus from hot marine sediments near Iceland and Ignicoccus pacificus from a hydrothermal vent system in the Pacific Ocean. This genus is unique among all archaea due to the unusual cell envelope, consisting of two membranes that enclose a large intermembrane compartment (IMC). I. hospitalis is the best studied member of this genus, mainly because it is the only known host for the potentially parasitic archaeon Nanoarchaeum equitansI. hospitalis grows chemolithoautotrophically, and its sole energy-yielding reaction is the reduction of elemental sulfur with molecular hydrogen, forming large amounts of hydrogen sulfide. This reaction generates an electrochemical gradient, which is used by the ATP synthase, located in the outer cellular membrane, to generate ATP inside the IMC. The genome of I. hospitalis encodes nine subunits of an A-type ATP synthase, which we could identify in the purified complex. Although the maximal in vitro activity of the I. hospitalis enzyme was measured around pH 6, the optimal stability of the A1AO complex seemed to be at pH 9. Interestingly, the soluble A1 subcomplexes of the different Ignicoccus species exhibited significant differences in their apparent molecular masses in native electrophoresis, although their behaviors in gel filtration and chromatography-mass spectrometry were very similar.IMPORTANCE The Crenarchaeota represent one of the major phyla within the Archaea domain. This study describes the successful purification of a crenarchaeal ATP synthase. To date, all information about A-type ATP synthases is from euryarchaeal enzymes. The fact that it has not been possible to purify this enzyme complex from a member of the Crenarchaeota until now points to significant differences in stability, possibly caused by structural alterations. Furthermore, the study subject I. hospitalis has a particular importance among crenarchaeotes, since it is the only known host of N. equitans The energy metabolism in this system is still poorly understood, and our results can help elucidate the unique relationship between these two microbes.

Dataset Information

The Dual Function of Reactive Oxygen/Nitrogen Species in Bioenergetics and Cell Death: The Role of ATP Synthase.

Publications

The Dual Function of Reactive Oxygen/Nitrogen Species in Bioenergetics and Cell Death: The Role of ATP Synthase.

Similar Datasets

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