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Kandel ER, Tauc L (1965)

Nitric Oxide 2002

Disruption in ER function or sudden accumulation of misfolded proteins triggers ER stress responses ( Lysosomal oxidative stress: Lysosomes, involved in cellular waste degradation, contain enzymes and metal ions that can generate oxidative compounds such as hydrogen peroxide and hydroxyl radicals under oxidative stress conditions ( Nuclear oxidative stress: The nucleus, housing genetic material, is susceptible to oxidative damage

Key target genes include those encoding components of the electron transport chain (ATP synthase subunits, cytochrome c), fatty acid oxidation enzymes (medium-chain acyl-CoA dehydrogenase, carnitine palmitoyltransferase 1), and transcription factors that amplify the metabolic signal (PGC-1 itself, NRF-1)