Osmolytes resist against harsh osmolarity: Something old something new

From the halophilic bacteria to human, cells have to survive under the stresses of harsh environments. Hyperosmotic stress is a process that triggers cell shrinkage, oxidative stress, DNA damage, and apoptosis and it potentially contributes to a number of human diseases. Remarkably, by high salts and organic solutes concentrations, a variety of organisms struggle with these conditions. Different strategies have been developed for cellular osmotic adaptations among which organic osmolyte synthesis/accumulation is a conserved once. Osmolytes are naturally occurring solutes used by cells of several halophilic (micro) organisms to preserve cell volume and function. In this review, the osmolytes diversity and their protective roles in harsh hyperosmolar environments from bacteria to human cells are highlighted. Moreover, it provides a close look at mammalian kidney osmoregulation at a molecular level. This review provides a concise view on the recent developments and advancements on the applications of osmolytes. Identification of disease-related osmolytes and their targeted-delivery may be used as a therapeutic measurement for treatment of the pathological conditions and the inherited diseases related to protein misfolding and aggregation. The molecular and cellular aspects of cell adaptation against harsh environmental osmolarity will benefit the development of effective drugs for many diseases. •Osmolytes are low-molecular-weight, relatively non-toxic, and water-soluble organic compounds.•Osmolytes preserve cellular osmotic balance, cell volume, and redox states against harsh conditions.•They have variety of applications in agriculture, biotechnology, molecular biology, and pharmacology.•There is a need for understanding the mechanisms of protein-stabilizing effects of osmolytes.