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Review
. 2020 Aug 6;9(8):1849.
doi: 10.3390/cells9081849.

Cross-Talk between NADPH Oxidase and Mitochondria: Role in ROS Signaling and Angiogenesis

Tohru Fukai  1   2 , Masuko Ushio-Fukai  1   3
Affiliations
Review

Cross-Talk between NADPH Oxidase and Mitochondria: Role in ROS Signaling and Angiogenesis

Tohru Fukai et al. Cells. .

Abstract

Angiogenesis, a new vessel formation from the pre-existing ones, is essential for embryonic development, wound repair and treatment of ischemic heart and limb diseases. However, dysregulated angiogenesis contributes to various pathologies such as diabetic retinopathy, atherosclerosis and cancer. Reactive oxygen species (ROS) derived from NADPH oxidase (NOX) as well as mitochondria play an important role in promoting the angiogenic switch from quiescent endothelial cells (ECs). However, how highly diffusible ROS produced from different sources and location can communicate with each other to regulate angiogenesis remains unclear. To detect a localized ROS signal in distinct subcellular compartments in real time in situ, compartment-specific genetically encoded redox-sensitive fluorescence biosensors have been developed. Recently, the intercellular communication, "cross-talk", between ROS derived from NOX and mitochondria, termed "ROS-induced ROS release", has been proposed as a mechanism for ROS amplification at distinct subcellular compartments, which are essential for activation of redox signaling. This "ROS-induced ROS release" may represent a feed-forward mechanism of localized ROS production to maintain sustained signaling, which can be targeted under pathological conditions with oxidative stress or enhanced to promote therapeutic angiogenesis. In this review, we summarize the recent knowledge regarding the role of the cross-talk between NOX and mitochondria organizing the sustained ROS signaling involved in VEGF signaling, neovascularization and tissue repair.

Keywords: NADPH oxidase; angiogenesis; endothelial cell; mitochondria; reactive oxygen species; redox signaling; vascular endothelial growth factor.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Role of reactive oxygen species (ROS) in angiogenesis in endothelial cells (ECs).
Figure 2
Figure 2
Generation and metabolism of ROS in ECs.
Figure 3
Figure 3
NOX isoforms expressed in endothelial cells.
Figure 4
Figure 4
Real-time imaging for cytosolic and mitochondrial redox status in single cell in response to VGEF.
Figure 5
Figure 5
Mitochondrial H2O2 production via the Nox4/Nox2/p-p66Shc axis.
Figure 6
Figure 6
NOX–mitochondria cross-talk in VGEF signaling and angiogenesis.
See this image and copyright information in PMC

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