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NRF2 inhibits lipid peroxidation and ferroptosis by activating antioxidant-responsive element (ARE)-containing genes involved in GSH production, glutamine metabolism, and iron metabolism (39, 40), but has no direct effect on GPX4 expression through binding the GPX4 promoter (41)

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The mitochondrion is formed by two membranes: the outer membrane and the inner membrane, which is highly folded, and the inner matrix is gel (approximately 50% water) [20]