Thiol switches in mitochondria: operation and physiological relevance

Abstract

Mitochondria are a major source of reactive oxygen species (ROS) in the cell, particularly of superoxide and hydrogen peroxide. A number of dedicated enzymes regulate the conversion and consumption of superoxide and hydrogen peroxide in the intermembrane space and the matrix of mitochondria. Nevertheless, hydrogen peroxide can also interact with many other mitochondrial enzymes, particularly those with reactive cysteine residues, modulating their reactivity in accordance with changes in redox conditions. In this review we will describe the general redox systems in mitochondria of animals, fungi and plants and discuss potential target proteins that were proposed to contain regulatory thiol switches.

The Roles of Mitochondrial Reactive Oxygen Species in Cellular Signaling and Stress Response in Plants

“…However, the reactivity of H 2 O 2 is also remarkably limited by kinetic competition and most thiols are not particularly reactive for H 2 O 2 within the cellular environment in the absence of catalysis. Exceptions, however, can be found in thiols of a small group of proteins that have been found enriched in mitochondria (Riemer et al, 2015). Particularly interesting are the thiol peroxidases, which have been recognized as among the most H 2 O 2 -reactive thiols in cells (Perkins et al, 2015) and are key players in H 2 O 2 detoxification in plants (Dietz, 2011).…”

“…To serve as a signal, this information must be conserved, perhaps by dividing regeneration into a rapid-turnover, high-flux antioxidant pathway and a slow-turnover, low-flux signaling pathway, with their relative contributions set by distinct biochemical properties. Once translated, the H 2 O 2 signal could then regulate downstream protein targets by a thiol switch or be further transduced by thiol-redox signaling (Riemer et al, 2015). This provides a means to quantify H 2 O 2 flux by 'counting' molecules detoxified at a specific location.…”

The mitochondrion: a central architect of copper homeostasis

“…91 Mitochondria are also major sources of superoxide anion and hydrogen peroxide, and a number of resident enzymes are dedicated to the conversion and consumption of these ROS. 92 However, it is well established that these ROS are more than simply by-products of metabolism and that they offer an essential means of regulating mitochondrial protein function via the post-translational modification (PTM) of reactive residues. 93 Elegant studies of other, non-mitochondrial proteins like OxyR further emphasize that direct modulation of a redox active cysteine via its sulfenylation, glutathionylation or nitrosylation allows for exquisite tuning of protein function.…”

Highlight: Dynamics of Thiol-Based Redox Switches

“…Is it possible that certain kinds of redoxins can also act as protein thiol oxidases? This field remains largely unexplored and awaits further discovery (Riemer et al, 2015).…”

“…In this issue of Biological Chemistry, members of the priority programme have reviewed different aspects pertaining to thiol switches in bacteria (Hillion and Antelmann, 2015), parasites (Rahbari et al, 2015), and different compartments of eukaryotic cells such as mitochondria (Riemer et al, 2015), chloroplasts (Dietz and Hell, 2015) or the endoplasmic reticulum (Suzuki and Schmitt, 2015). The functional relevance of some thiol switches described in this collection is relatively well understood, for example in the case of the H 2 O 2 -sensing bacterial transcription factor OxyR (Hillion and Antelmann, 2015), whereas in others it is more elusive such as in the context of T cell receptor signalling (Simeoni and Bogeski, 2015) or ROXY-mediated signal transduction in plants (Gutsche et al, 2015).…”