VRAC: unravelling the complexity of LRRC8 subunit regulation by oxidation

Friard, Jonas; Rubera, Isabelle; Duranton, Christophe

doi:10.1113/jp275188

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Regulation Of Lrrc8/vrac Activity By Oxidation and Reduction1

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2024

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“…This allowed to clarify direct effects of oxidizing and reducing agents on LRRC8-mediated VRAC channel function. Gradogna and collaborators shed light on the modulation of VRAC currents by oxidation [26,62]. Heterologous co-expression of LRRC8A/C, A/D and A/E isoforms in Xenopus oocytes resulted in currents with differential sensitivity to the oxidant Chloramine-T (Chlor-T) as well as tert-butyl hydroperoxide (TBHP).…”

Section: Regulation Of Lrrc8/vrac Activity By Oxidation and Reductionmentioning

confidence: 99%

VRAC Channels and the Cellular Redox Balance

Morabito¹,

Spinelli²,

Marino³

et al. 2024

Physiology

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Volume-regulated anion channels (VRAC) are mainly involved in the regulated transport of osmolytes such as ions or small organic compounds across the plasma membrane during anisosmotic cell swelling. However, they also play additional roles in various pathophysiological processes, such as the transport of metabolites and drugs, extracellular signal transduction and anti-cancer drug resistance. These channels are formed by heteromers of LRRC8 proteins, of which LRRC8A is the essential subunit that combines with its paralogs LRRC8B–E to form hexameric complexes. Despite the extensive research devoted to the understanding of VRACs functions, different aspects of these channels are still to be characterized in depth. In this chapter, recent findings concerning the involvement of VRAC channels in the cellular redox balance will be summarized. Also, their relevance as potential targets of antioxidant therapies will be discussed.

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Section: Regulation Of Lrrc8/vrac Activity By Oxidation and Reductionmentioning

confidence: 99%