Caveolin-1 controls mitochondrial damage and ROS production by regulating fission - fusion dynamics and mitophagy

Jiang, Ying; Krantz, Sarah; Qin, Xiang; Li, Shun; Gunasekara, Hirushi; Kim, Young-Mee; Zimnicka, Adriana M.; Bae, Misuk; Ma, Ke; Tóth, Péter T.; Hu, Ying; Shajahan-Haq, Ayesha N.; Patel, Hemal H.; Gentile, Sandro; Rehman, Jalees; Liu, Yiyao; Minshall, Richard D.

doi:10.1016/j.redox.2022.102304

Cited by 59 publications

(39 citation statements)

References 62 publications

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“…Some authors have reported on the presence of CAV1 in mitochondria [ 48 ] and others in mitochondria-associated ER membranes [ 49 , 50 ]. Additionally, CAV1 appears necessary for mitochondrial functionality in normal cells [ 51 ], but, in cancer cells, mitochondrial CAV1 enhances cell survival in response to stress [ 52 , 53 ] and inhibits mitochondrial respiration increasing tumor malignancy. As mentioned, our results here demonstrate that the elevated expression of CAV1 reduces mitochondrial respiration in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Dysfunction and the Glycolytic Switch Induced by Caveolin-1 Phosphorylation Promote Cancer Cell Migration, Invasion, and Metastasis

Díaz-Valdivia

Simón

Díaz

et al. 2022

Cancers

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Cancer cells often display impaired mitochondrial function, reduced oxidative phosphorylation, and augmented aerobic glycolysis (Warburg effect) to fulfill their bioenergetic and biosynthetic needs. Caveolin-1 (CAV1) is a scaffolding protein that promotes cancer cell migration, invasion, and metastasis in a manner dependent on CAV1 phosphorylation on tyrosine-14 (pY14). Here, we show that CAV1 expression increased glycolysis rates, while mitochondrial respiration was reduced by inhibition of the mitochondrial complex IV. These effects correlated with increased reactive oxygen species (ROS) levels that favored CAV1-induced migration and invasion. Interestingly, pY14-CAV1 promoted the metabolic switch associated with increased migration/invasion and augmented ROS-inhibited PTP1B, a phosphatase that controls pY14 levels. Finally, the glycolysis inhibitor 2-deoxy-D-glucose reduced CAV1-enhanced migration in vitro and metastasis in vivo of murine melanoma cells. In conclusion, CAV1 promotes the Warburg effect and ROS production, which inhibits PTP1B to augment CAV1 phosphorylation on tyrosine-14, thereby increasing the metastatic potential of cancer cells.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial Dysfunction and the Glycolytic Switch Induced by Caveolin-1 Phosphorylation Promote Cancer Cell Migration, Invasion, and Metastasis

Díaz-Valdivia

Simón

Díaz

et al. 2022

Cancers

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“…The activation of Kv11.1 is not enough to kill cancer cells in situ. Furthermore, a recent study by our group showed that the dephosphorylation of Cav-1 promotes mitophagy and therefore may increase cancer cell survival by eliminating damaged mitochondria [ 30 ]. Taken together, these studies indicate that the Kv11.1 activation-dependent dephosphorylation of Cav-1 arrests cancer cell migration, and thereby substantiates its potential clinical use for the prevention of metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…Caveolin-1 adenovirus was generated in the Viral Vector Core Laboratory at UCSD as described [ 30 ]. Full-length Homo sapiens caveolin-1 was used as a template to generate C-terminal CFP-tagged caveolin-1 (Cav-1-CFP), as well as the phospho-defective and mimicking mutants Y14F and Y14D [ 31 ].…”

Section: Methodsmentioning

confidence: 99%

Pharmacological Activation of Potassium Channel Kv11.1 with NS1643 Attenuates Triple Negative Breast Cancer Cell Migration by Promoting the Dephosphorylation of Caveolin-1

Jiang

Senyuk

et al. 2022

Cells

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The prevention of metastasis is a central goal of cancer therapy. Caveolin-1 (Cav-1) is a structural membrane and scaffolding protein shown to be a key regulator of late-stage breast cancer metastasis. However, therapeutic strategies targeting Cav-1 are still lacking. Here, we demonstrate that the pharmacological activation of potassium channel Kv11.1, which is uniquely expressed in MDA-MB-231 triple negative breast cancer cells (TNBCs) but not in normal MCF-10A cells, induces the dephosphorylation of Cav-1 Tyr-14 by promoting the Ca2+-dependent stimulation of protein tyrosine phosphatase 1B (PTP1B). Consequently, the dephosphorylation of Cav-1 resulted in its disassociation from β-catenin, which enabled the accumulation of β-catenin at cell borders, where it facilitated the formation of cell–cell adhesion complexes via interactions with R-cadherin and desmosomal proteins. Kv11.1 activation-dependent Cav-1 dephosphorylation induced with NS1643 also reduced cell migration and invasion, consistent with its ability to regulate focal adhesion dynamics. Thus, this study sheds light on a novel pharmacological mechanism of promoting Cav-1 dephosphorylation, which may prove to be effective at reducing metastasis and promoting contact inhibition.

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“…Lanthanum oxide, cerium dioxide, europium oxide, and manganese also triggered autophagy [ 75 ]. Caveolin 1 (CAV1) is an important membrane protein for cell membrane trafficking and autophagy [ 76 ]. Additionally, biodegradable ferric phosphate nanosheets are coated with doxorubicin for targeted tumor eradication via an autophagy inhibition-enhanced apoptosis/ferroptosis pathway [ 77 ].…”

Section: Targeting Autophagy Modulation To Eliminate Environmental Su...mentioning

confidence: 99%

The Emerging Role of Autophagy as a Target of Environmental Pollutants: An Update on Mechanisms

Rahman

Parvez

et al. 2023

Toxics

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Autophagy is an evolutionarily conserved cellular system crucial for cellular homeostasis that protects cells from a broad range of internal and extracellular stresses. Autophagy decreases metabolic load and toxicity by removing damaged cellular components. Environmental contaminants, particularly industrial substances, can influence autophagic flux by enhancing it as a protective response, preventing it, or converting its protective function into a pro-cell death mechanism. Environmental toxic materials are also notorious for their tendency to bioaccumulate and induce pathophysiological vulnerability. Many environmental pollutants have been found to influence stress which increases autophagy. Increasing autophagy was recently shown to improve stress resistance and reduce genetic damage. Moreover, suppressing autophagy or depleting its resources either increases or decreases toxicity, depending on the circumstances. The essential process of selective autophagy is utilized by mammalian cells in order to eliminate particulate matter, nanoparticles, toxic metals, and smoke exposure without inflicting damage on cytosolic components. Moreover, cigarette smoke and aging are the chief causes of chronic obstructive pulmonary disease (COPD)-emphysema; however, the disease’s molecular mechanism is poorly known. Therefore, understanding the impacts of environmental exposure via autophagy offers new approaches for risk assessment, protection, and preventative actions which will counter the harmful effects of environmental contaminants on human and animal health.

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Caveolin-1 controls mitochondrial damage and ROS production by regulating fission - fusion dynamics and mitophagy

Cited by 59 publications

References 62 publications

Mitochondrial Dysfunction and the Glycolytic Switch Induced by Caveolin-1 Phosphorylation Promote Cancer Cell Migration, Invasion, and Metastasis

Mitochondrial Dysfunction and the Glycolytic Switch Induced by Caveolin-1 Phosphorylation Promote Cancer Cell Migration, Invasion, and Metastasis

Pharmacological Activation of Potassium Channel Kv11.1 with NS1643 Attenuates Triple Negative Breast Cancer Cell Migration by Promoting the Dephosphorylation of Caveolin-1

The Emerging Role of Autophagy as a Target of Environmental Pollutants: An Update on Mechanisms

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