Dynamics of intracellular and intercellular redox communication
Helmut Sies
Abstract
Cell and organ metabolism is organized through various signaling mechanisms, including redox, Ca 2+ , kinase and electrochemical pathways. Redox signaling operates at multiple levels, from interactions between individual molecules in their microenvironment to communication among subcellular organelles, single cells, organs, and the entire organism. Redox communication is a dynamic and ongoing spatiotemporal process. This article focuses on hydrogen peroxide (H 2 O 2 ), a key second messenger that targets redox-active protein cysteine thiolates. H 2 O 2 gradients across cell membranes are controlled by peroxiporins, specialized aquaporins. Redox-active endosomes, known as redoxosomes, form at the plasma membrane. Cell-to-cell redox communication involves direct contacts, such as per gap junctions that connect cells for transfer of molecules via connexons. Moreover, signaling occurs through the release of redox-active molecules and enzymes into the surrounding space, as well as through various extracellular vesicles (EVs) that transport these signals to nearby or distant target cells. • Organization of cell metabolism into subcellular organelles utilizes multiple communication modes for dynamic control. • Focus is on H 2 O 2 as a major pleiotropic agent in redox communication within and between cellular microenvironments. • Maintenance of the cellular H 2 O 2 steady state landscape is a continuously ongoing dynamic challenge. • Membraneless organelles (biomolecular condensates) modulate redox communication. • Adjacent or distant cells are redox-orchestrated by redoxosomes, exosomes, peroxiporins and various gating mechanisms.