Fig. 8.

Summary of the possible biological roles of the 2′,3′-cGMP-guanosine and 2′,3′-cAMP-adenosine pathways. Tissue injury is known to trigger degradation of RNA, which is the main mechanism for production of nucleoside 2′,3′-cyclic monophosphates. 2′,3′-cAMP is known to facilitate opening of mitochondrial permeability transition pores (mPTPs) and, thereby, induce mitophagy and apoptosis (which can be beneficial or harmful, depending on context). In addition, 2′,3′-cAMP is known to bind to proteins that form stress granules (SGs) and, thereby, triggers SG formation (a protective mechanism). 2′,3′-cAMP may have yet additional unknown (?) effects. Although 2′,3′-cGMP does not significantly affect mPTPs and SGs, it is likely that this noncanonical nucleotide has other unknown (?) direct effects on cell biology. Both 2′,3′-cAMP and 2′,3′-cGMP are converted to their corresponding monophosphate metabolites, which may also have unknown (?) biological effects. 2′-AMP and 3′-AMP are converted to adenosine, whereas 2′-GMP and 3′-GMP are metabolized to guanosine. Both adenosine and guanosine are known to provide organ and cell protection. Additionally, guanosine is known to elevate extracellular levels of adenosine.