NOX4 functions as a mitochondrial energetic sensor coupling cancer metabolic reprogramming to drug resistance

Shanmugasundaram, Karthigayan; Nayak, B. K.; Friedrichs, William E.; Kaushik, Dharam; Rodríguez, Ronald; Block, Karen

doi:10.1038/s41467-017-01106-1

Cited by 176 publications

(161 citation statements)

References 58 publications

Supporting

Mentioning

154

Contrasting

Unclassified

Order By: Relevance

“…macrophages and reducing NOX4-mediated ROS production is known to be protective in several disease conditions, such as cardiac ischemia/reperfusion injuries, diabetes, and Streptococcus pneumoniae infection (8,35,36). Here, we show that NOX4-derived ROS are critical for profibrotic cytokine production, and reducing ROS production by deleting NOX4 in macrophages can decrease profibrotic polarization.…”

Section: Discussionmentioning

confidence: 60%

NOX4 modulates macrophage phenotype and mitochondrial biogenesis in asbestosis

He¹,

Larson‐Casey²,

Davis³

et al. 2019

JCI Insight

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 60%

NOX4 modulates macrophage phenotype and mitochondrial biogenesis in asbestosis

He¹,

Larson‐Casey²,

Davis³

et al. 2019

JCI Insight

View full text Add to dashboard Cite

“…Under normal conditions, ATP binds allosterically to NOX4 through Walker A ATP-binding domain, keeping NOX4-derived ROS production low. However, certain cellular events, such as cancer, which switch ATP production to aerobic glycolysis in the cytosol, lead to a reduction of the ATP levels in the mitochondria, thereby relieving this inhibition and leading to NOX4derived ROS production (Shanmugasundaram et al 2017).…”

Section: Thyroid Ros-generating Systems: the Nadph Oxidases And The Mmentioning

confidence: 99%

Oxidative stress in thyroid carcinomas: biological and clinical significance

Hassani

Buffet

Leboulleux

et al. 2019

Endocrine-Related Cancer

View full text Add to dashboard Cite

At physiological concentrations, reactive oxygen species (ROS), including superoxide anions and H2O2, are considered as second messengers that play key roles in cellular functions, such as proliferation, gene expression, host defence and hormone synthesis. However, when they are at supraphysiological levels, ROS are considered potent DNA-damaging agents. Their increase induces oxidative stress, which can initiate and maintain genomic instability. The thyroid gland represents a good model for studying the impact of oxidative stress on genomic instability. Indeed, one particularity of this organ is that follicular thyroid cells synthesise thyroid hormones through a complex mechanism that requires H2O2. Because of their detection in thyroid adenomas and in early cell transformation, both oxidative stress and DNA damage are believed to be neoplasia-preceding events in thyroid cells. Oxidative DNA damage is, in addition, detected in the advanced stages of thyroid cancer, suggesting that oxidative lesions of DNA also contribute to the maintenance of genomic instability during the subsequent phases of tumourigenesis. Finally, ionizing radiation and the mutation of oncogenes, such as RAS and BRAF, play a key role in thyroid carcinogenesis through separate and unique mechanisms: they upregulate the expression of two distinct ‘professional’ ROS-generating systems, the NADPH oxidases DUOX1 and NOX4, which cause DNA damage that may promote chromosomal instability, tumourigenesis and dedifferentiation.

show abstract

“…NOX family consists of five isoforms including NOX1, NOX2, NOX3, NOX4 and NOX5, which accelerate ROS production in the vasculature [23][24][25][26][27]. In this scenario, we shift the concept to NOX4 as a critical driver for various renal disorders since NOX4 is most plentiful in kidney [28][29][30].…”

Section: Nox Signalingmentioning

confidence: 99%

Redox signaling in aging kidney and opportunity for therapeutic intervention through natural products

Chen

et al. 2019

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Kidney diseases are serious public problems with high morbidity and mortality in the general population and heavily retard renal function with aging regardless of the cause. Although myriad strategies have been assigned to prevent or harness disease progression, unfortunately, thus far, there is a paucity of effective therapies partly due to an insufficient knowledge of underlying pathological mechanisms, indicating deeper studies are urgently needed. Additionally, natural products are increasingly recognized as an alternative source for disease intervention owing to the potent safety and efficacy, which might be exploited for novel drug discovery. In this review, we primarily expatiate the new advances on mediators that might be amenable to targeting aging kidney and kidney diseases, including nicotinamide adenine dinucleotide phosphate oxidase (NOX), transforming growth factor-β (TGF-β), renin-angiotensin system (RAS), nuclear factor-erythroid 2 related factor 2 (Nrf2), peroxisome proliferator-activated γ receptor (PPARγ), advanced glycation endproducts (AGEs) as well as microRNAs and vitagenes. Of note, we conclude by highlighting some natural products which have the potential to facilitate the development of novel treatment for patients with myriad renal diseases.

show abstract

NOX4 functions as a mitochondrial energetic sensor coupling cancer metabolic reprogramming to drug resistance

Cited by 176 publications

References 58 publications

NOX4 modulates macrophage phenotype and mitochondrial biogenesis in asbestosis

NOX4 modulates macrophage phenotype and mitochondrial biogenesis in asbestosis

Oxidative stress in thyroid carcinomas: biological and clinical significance

Redox signaling in aging kidney and opportunity for therapeutic intervention through natural products

Contact Info

Product

Resources

About