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Under conditions of compromised mitochondrial function, the proton-motive force falls below the threshold required for ATP synthesis and the activity of ATP synthase can actually reverse such that it hydrolyzes ATP to pump protons back into the inner membrane space

On the right, proposed solutions are highlighted, including the use of patient-derived cirrhotic organoids and humanized mouse models to evaluate safety, the development of proteolysis-targeted chimeras (PROTACs) and other structure-based inhibitors with targeted delivery systems, the integration of NFE2L2 /Kelch-like ECH-associated protein 1 ( KEAP1 ) genotyping with immunohistochemistry and transcriptomics for accurate patient stratification, and the validation of real-time NRF2 activity markers for therapy monitoring

p53 in the Cytoplasm: A Question of Overkill

Astaxanthin supplementation enhances metabolic adaptation with aerobic training in the elderly