Evidence map›Paper›PMID 32079324›Full record

ReviewBiomolecules2020

Regulation of Nrf2 by Mitochondrial Reactive Oxygen Species in Physiology and Pathology.

Shuya Kasai, Sunao Shimizu, Yota Tatara, Junsei Mimura, Ken Itoh

Abstract readReview
In one paragraph

Review in Biomolecules, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 315 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
315citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

315 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
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  6. Journal of enzyme inhibition and medicinal chemistry · 2026
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255 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Shuya KasaiDepartment of Stress Response Science, Center for Advanced Medical Research, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
Sunao ShimizuDepartment of Stress Response Science, Center for Advanced Medical Research, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
Yota TataraDepartment of Glycotechnology, Center for Advanced Medical Research, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
Junsei MimuraDepartment of Stress Response Science, Center for Advanced Medical Research, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
Ken ItohDepartment of Stress Response Science, Center for Advanced Medical Research, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Reactive oxygen species (ROS) are byproducts of aerobic respiration and signaling molecules that control various cellular functions. Nrf2 governs the gene expression of endogenous antioxidant synthesis and ROS-eliminating enzymes in response to various electrophilic compounds that inactivate the negative regulator Keap1. Accumulating evidence has shown that mitochondrial ROS (mtROS) activate Nrf2, often mediated by certain protein kinases, and induce the expression of antioxidant genes and genes involved in mitochondrial quality/quantity control. Mild physiological stress, such as caloric restriction and exercise, elicits beneficial effects through a process known as "mitohormesis." Exercise induces NOX4 expression in the heart, which activates Nrf2 and increases endurance capacity. Mice transiently depleted of SOD2 or overexpressing skeletal muscle-specific UCP1 exhibit Nrf2-mediated antioxidant gene expression and PGC1α-mediated mitochondrial biogenesis. ATF4 activation may induce a transcriptional program that enhances NADPH synthesis in the mitochondria and might cooperate with the Nrf2 antioxidant system. In response to severe oxidative stress, Nrf2 induces Klf9 expression, which represses mtROS-eliminating enzymes to enhance cell death. Nrf2 is inactivated in certain pathological conditions, such as diabetes, but Keap1 down-regulation or mtROS elimination rescues Nrf2 expression and improves the pathology. These reports aid us in understanding the roles of Nrf2 in pathophysiological alterations involving mtROS.

Indexed as

Oxidative StressAnimalsHumansKruppel-Like Transcription FactorsMitochondriaNF-E2-Related Factor 2Reactive Oxygen SpeciesTranscriptional ActivationKLF9 protein, humanKruppel-Like Transcription FactorsNFE2L2 protein, humanNF-E2-Related Factor 2Reactive Oxygen SpeciesATF4Keap1Klf9mitochondrial ROSNrf2PGC1αSirt6

Identifiers

PMID32079324
PMCPMC7072240

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.