The Nrf2-ARE transcriptional pathway plays an important role amongst cellular defence systems regulating and ensuring adequacy of redox responses and oxidant signalling factors. Hepatocyte cellular death and injury is a prominent feature underlying liver pathologies. Diverse endogenous molecules and targets contribute to the outcome of cell survival and the consequent mode of cell death. Several research efforts focused on the confirmation of Nrf2 presence in cell death and its vital necessity against cell compromise, however, little they comprehend of such participation. Hepatocyte cell death modes discussed in this review including autophagy, apoptosis, necrosis, ferroptosis, pyroptosis, fibrosis and others, vary in response of the stimuli burdened. The current review presents a handful of highlights and crosstalk involved in the communication of Nrf2 signalling network with the "up to date" reported hepatocyte cell death modes and their underling mechanisms, and addressing key cellular networks of hepatocyte fate, through a perspective of Nrf2 as a critical transcriptional factor. Collectively, labelling the cross-transduction of Nrf2-ARE axis with key cell execution pathways could provide insights to therapeutic interventions and better research outcomes.
Keywords: Autophagy; Ferroptosis; NF-κB; PPARγ; Pyroptosis; SREBF1.
© 2022. The Author(s), under exclusive licence to Springer Nature B.V.