Cross-Regulation of the Cellular Redox System, Oxygen, and Sphingolipid Signalling.

Huwiler, Andrea; Beck, Karl-Friedrich; Pfeilschifter, Josef (2023). Cross-Regulation of the Cellular Redox System, Oxygen, and Sphingolipid Signalling. Metabolites, 13(3) MDPI 10.3390/metabo13030426

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Redox-active mediators are now appreciated as powerful molecules to regulate cellular dynamics such as viability, proliferation, migration, cell contraction, and relaxation, as well as gene expression under physiological and pathophysiological conditions. These molecules include the various reactive oxygen species (ROS), and the gasotransmitters nitric oxide (NO∙), carbon monoxide (CO), and hydrogen sulfide (H2S). For each of these molecules, direct targets have been identified which transmit the signal from the cellular redox state to a cellular response. Besides these redox mediators, various sphingolipid species have turned out as highly bioactive with strong signalling potential. Recent data suggest that there is a cross-regulation existing between the redox mediators and sphingolipid molecules that have a fundamental impact on a cell's fate and organ function. This review will summarize the effects of the different redox-active mediators on sphingolipid signalling and metabolism, and the impact of this cross-talk on pathophysiological processes. The relevance of therapeutic approaches will be highlighted.

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