Transient receptor potential (TRP) channels: Biosensors for redox environmental stimuli and cellular status

Transient receptor potential (TRP) channels are a family of cation channels that depolarizes the membrane potential and regulates intracellular concentrations of cations such as Ca²⁺. TRP channels are also known to function as "biosensors" to detect changes of the surrounding environment and cellular status. Lines of evidence have unveiled that numerous proteins are subject to redox modification and subsequent signaling. For example, TRPM2, TRPC5, TRPV1, and TRPA1 are known as redox sensors activated by hydrogen peroxide (H₂O₂), nitric oxide (NO), and electrophiles. Thus, these channels facilitate the influx of cations which in turn triggers the appropriate cellular responses against environmental redox stimuli and cellular redox status. In this review, we focus on the recent findings regarding the functions of TRP channels in relation to other ion channels, and other proteins which also go through redox modification of cysteine (Cys) residues. We aim to understand the structural and molecular basis of the redox-sensing mechanisms of TRP channels in exerting various functions under physiological conditions as well as pathological conditions such as cancer malignancy. Their future potential as drug targets will also be discussed.