Sulforaphane Activates a lysosome-dependent transcriptional program to mitigate oxidative stress.

Autophagy
Dan LiHaoxing Xu

Abstract

Oxidative stress underlies a number of pathological conditions, including cancer, neurodegeneration, and aging. Antioxidant-rich foods help maintain cellular redox homeostasis and mitigate oxidative stress, but the underlying mechanisms are not clear. For example, sulforaphane (SFN), an electrophilic compound that is enriched in cruciferous vegetables such as broccoli, is a potent inducer of cellular antioxidant responses. NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2), a transcriptional factor that controls the expression of multiple detoxifying enzymes through antioxidant response elements (AREs), is a proposed target of SFN. NFE2L2/NRF2 is a target gene of TFEB (transcription factor EB), a master regulator of autophagic and lysosomal functions, which we show here to be potently activated by SFN. SFN induces TFEB nuclear translocation via a Ca2+-dependent but MTOR (mechanistic target of rapamycin kinase)-independent mechanism through a moderate increase in reactive oxygen species (ROS). Activated TFEB then boosts the expression of genes required for autophagosome and lysosome biogenesis, which are known to facilitate the clearance of damaged mitochondria. Notably, TFEB activity is required for SFN-induced protection against...Continue Reading

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Citations

Aug 3, 2021·Oxidative Medicine and Cellular Longevity·Dan LiShixue Cheng
Oct 5, 2021·EMBO Molecular Medicine·Antonietta TaralloGiancarlo Parenti

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Software Mentioned

Metamorph
EasyRatioPro
NIH Image J
MetaMorph Advanced Imaging
Maxchelator

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