The multifaceted role of Nrf2 in mitochondrial function
TLDR
Small molecule activators of Nrf2 support mitochondrial integrity by promoting mitophagy and conferring resistance to oxidative stress-mediated permeability transition, with implications for stem cell self-renewal, cardiomyocyte regeneration, and neural stem/progenitor cell survival.About:
This article is published in Current Opinion in Toxicology.The article was published on 2016-12-01 and is currently open access. It has received 253 citations till now. The article focuses on the topics: Mitochondrial ROS & Mitophagy.read more
Citations
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Mechanisms of mitophagy in cellular homeostasis, physiology and pathology.
Konstantinos Palikaras,Konstantinos Palikaras,Eirini Lionaki,Nektarios Tavernarakis,Nektarios Tavernarakis +4 more
TL;DR: In this Review, Tavernarakis and colleagues describe recent advances in delineating the molecular mechanisms that mediate mitophagy, and discuss the complex roles of this pathway in physiological and pathological contexts.
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Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases
Antonio Cuadrado,Ana I. Rojo,Geoffrey Wells,John D. Hayes,Sharon P. Cousin,William L. Rumsey,Attucks Otis Clinton,Stephen Franklin,Anna-Liisa Levonen,Thomas W. Kensler,Albena T. Dinkova-Kostova,Albena T. Dinkova-Kostova +11 more
TL;DR: An overview of the physiological and pathological roles of NRF2 is provided, emerging pharmacological modulators of theNRF2–KEAP1 axis are presented and associated drug development challenges are highlighted.
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Targeting the KEAP1-NRF2 System to Prevent Kidney Disease Progression
TL;DR: Genetic or pharmacological enhancement of NRF2 activity in the renal tubules significantly ameliorates damage related to AKI and prevents AKI progression to chronic kidney disease (CKD) by reducing oxidative stress.
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Regulation of Mitochondrial Biogenesis as a Way for Active Longevity: Interaction Between the Nrf2 and PGC-1α Signaling Pathways
TL;DR: In this review, recent data is summarized on the Nrf2 role in mitochondrial biogenesis and its interaction with PGC-1α in the context of extending longevity.
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Reactive Oxygen Species and Mitochondrial Dynamics: The Yin and Yang of Mitochondrial Dysfunction and Cancer Progression
TL;DR: The latest findings on the intricate relationship between mitochondrial dynamics and ROS production are reviewed, focusing mainly on its role in malignant disease.
References
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An nrf2/small maf heterodimer mediates the induction of phase ii detoxifying enzyme genes through antioxidant response elements
Ken Itoh,Tomoki Chiba,Satoru Takahashi,Tetsuro Ishii,Kazuhiko Igarashi,Yasutake Katoh,Tatsuya Oyake,Norio Hayashi,Kimihiko Satoh,Ichiro Hatayama,Masayuki Yamamoto,Yo-ichi Nabeshima +11 more
TL;DR: It is demonstrated that Nrf2 is essential for the transcriptional induction of phase II enzymes and the presence of a coordinate transcriptional regulatory mechanism for phase II enzyme genes and the nrf2-deficient mice may prove to be a very useful model for the in vivo analysis of chemical carcinogenesis and resistance to anti-cancer drugs.
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Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain
Ken Itoh,Nobunao Wakabayashi,Yasutake Katoh,Tetsuro Ishii,Kazuhiko Igarashi,James Douglas Engel,James Douglas Engel,Masayuki Yamamoto +7 more
TL;DR: It is postulate that Keap1 and Nrf2 constitute a crucial cellular sensor for oxidative stress, and together mediate a key step in the signaling pathway that leads to transcriptional activation by this novel NRF2 nuclear shuttling mechanism.
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Cell Survival Responses to Environmental Stresses Via the Keap1-Nrf2-ARE Pathway
TL;DR: The development of Nrf2 knockout mice has provided key insights into the toxicological importance of this pathway, and this review highlights the key elements in this adaptive response to protection against acute and chronic cell injury provoked by environmental stresses.
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PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1
Sven Geisler,Kira M. Holmström,Diana Skujat,Fabienne C. Fiesel,Oliver Rothfuss,Philipp J. Kahle,Wolfdieter Springer +6 more
TL;DR: Functional links between PINK1, Parkin and the selective autophagy of mitochondria, which is implicated in the pathogenesis of Parkinson's disease, are provided.
Journal Article
Free Radicals, Antioxidants in Disease and Health
TL;DR: This mini-review deals with the taxonomy, the mechanisms of formation and catabolism of the free radicals, it examines their beneficial and deleterious effects on cellular activities, and it highlights the potential role of the antioxidants in preventing and repairing damages caused by oxidative stress.