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Review
. 2024 Sep;598(17):2092-2105.
doi: 10.1002/1873-3468.14993. Epub 2024 Aug 8.

Nrf2 as a regulator of energy metabolism and mitochondrial function

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Free article
Review

Nrf2 as a regulator of energy metabolism and mitochondrial function

Alina Luchkova et al. FEBS Lett. 2024 Sep.
Free article

Abstract

Nuclear factor erythroid-2-related factor 2 (Nrf2) is essential for the control of cellular redox homeostasis. When activated, Nrf2 elicits cytoprotective effects through the expression of several genes encoding antioxidant and detoxifying enzymes. Nrf2 can also improve antioxidant defense via the pentose phosphate pathway by increasing NADPH availability to regenerate glutathione. Microarray and genome-wide localization analyses have identified many Nrf2 target genes beyond those linked to its redox-regulatory capacity. Nrf2 regulates several intermediary metabolic pathways and is involved in cancer cell metabolic reprogramming, contributing to malignant phenotypes. Nrf2 also modulates substrate utilization for mitochondrial respiration. Here we review the experimental evidence supporting the essential role of Nrf2 in the regulation of energy metabolism and mitochondrial function.

Keywords: Nrf2; energy metabolism; metabolic reprogramming; mitochondria; oxidative stress; redox signaling.

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References

    1. Moi P, Chan K, Asunis I, Cao A and Kan YW (1994) Isolation of NF‐E2‐related factor 2 (Nrf2), a NF‐E2‐like basic leucine zipper transcriptional activator that binds to the tandem NF‐E2/AP1 repeat of the beta‐globin locus control region. Proc Natl Acad Sci USA 91, 9926–9930.
    1. Yamamoto M, Kensler TW and Motohashi H (2018) The KEAP1‐NRF2 system: a thiol‐based sensor‐effector apparatus for maintaining redox homeostasis. Physiol Rev 98, 1169–1203.
    1. Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K, Engel JD and Yamamoto M (1999) Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino‐terminal Neh2 domain. Genes Dev 13, 76–86.
    1. Malhotra D, Portales‐Casamar E, Singh A, Srivastava S, Arenillas D, Happel C, Shyr C, Wakabayashi N, Kensler TW, Wasserman WW et al. (2010) Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP‐Seq profiling and network analysis. Nucleic Acids Res 38, 5718–5734.
    1. Suzuki T, Takahashi J and Yamamoto M (2023) Molecular basis of the KEAP1‐NRF2 signaling pathway. Mol Cells 46, 133–141.

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