Fig 1: An illustrative model of the biphasic Janus role of microRNA-210 (miR-210) in modulating apoptotic cell death during cellular hypoxia and reoxygenation phases. (A) miR-210 inhibited the hypoxia-induced intrinsic apoptosis pathway (1). miR-210 inhibited the hypoxia-induced cytochrome c translocation from the mitochondria to the cytosol (2), resulting in a decrease of the abundance of the apoptosome complex (3), the protein complex that serves as the rate-limiting factor in the caspase cascade activation. The decrease in the abundance of the apoptosome complex translates into a decrease flux in caspase-9 activation (not determined in this study) that results in the attenuation of the downstream effector, caspase-3 activity (4). The miR-210-elicited mitigation in hypoxia-induced caspase-3 activity culminated in the attenuation of hypoxia-induced apoptotic cell death (5). (B) miR-210 augmented the hypoxia-reoxygenation (H-R)-induced flux through the intrinsic apoptosis pathway (6), as well as the extrinsic apoptosis pathway (9). miR-210 exacerbated the H-R-induced cytochrome c release into the cytosol (7), resulting in an increase in the apoptosome complex formation (8). miR-210 also fostered the H-R-induced DISC-IIa complex formation (9), the protein complex that characterizes the rate-limiting step in the flux through extrinsic apoptosis pathway. The increase in the abundance of the DISC-IIa complex translated into an increase flux in caspase-8 activation (10). The miR-210 exacerbation of the H-R-induced apoptosome complex formation (8) and caspase-8 activation (10) resulted in a significant increase in caspase-3 activity (11,12). The miR-210-elicited exacerbation of H-R-induced caspase-3 activity culminated in the augmentation of H-R-induced apoptotic cell death (13). This illustration was created in BioRender.com and adapted from “Apoptosis Extrinsic and Intrinsic Pathways” by BioRender.com (2021). Retrieved from https://app.biorender.com/illustrations/61826429218a0b00a6f7b838 on 3 November 2021.