Drp1 regulates mitochondrial morphology and cell proliferation in cutaneous squamous cell carcinoma

Kitamura, Shinya; Yanagi, Teruki; Imafuku, Kimiaki; Hata, Hiroo; Abe, Riichiro; Shimizu, Hiroshi

doi:10.1016/j.jdermsci.2017.08.004

Cited by 39 publications

(20 citation statements)

References 28 publications

(53 reference statements)

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“…, IFN225,26 and Drp146 .Intriguingly, likewise for myosin-Va knockdown, Drp1 knockdown has also been shown to result in diminished tumorigenesis and features, such as increased OXPHOS and low clonogenic ability4,5,47 .Our data show that myosin-Va interacts with Spire1C and overexpression of Spire1C increases myosin-Va localization to mitochondria. Recently, non-mitochondrial Spire splice isoforms have been shown to interact with myosin-V motors32 .…”

supporting

confidence: 57%

A novel role for Myosin-Va in mitochondrial fission

Araujo

Silva-Júnior

Zhang

et al. 2019

Preprint

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In cancer cells metabolic changes and mitochondrial morphology are coupled. It is known that the cytoskeleton and molecular motors are directly involved in regulating mitochondrial morphology. Here we show that myosin-Va, an actin-based molecular motor, is required for the malignant properties of melanoma cells and localizes to mitochondria in these cells. Knockdown of myosin-Va increases cellular respiration rates and ROS production and decreases glucose uptake and lactate secretion. In addition, knockdown of myosin-Va results in reduced mitochondrial fission and correspondingly elongated mitochondria. We show that myosin-Va interacts with the mitochondrial outer membrane protein Spire1C, an actin-regulatory protein implicated in mitochondrial fission, and that Spire1C recruits myosin-Va to mitochondria. Finally, we show that during mitochondrial fission myosin-Va localization to mitochondria increases, and that myosin-Va localizes to mitochondrial fission sites immediately adjacent to Drp1 punctae. We conclude that myosin-Va facilitates mitochondrial fission. These data implicate myosin-Va as a target for the Warburg effect in melanoma cells.

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supporting

confidence: 57%

A novel role for Myosin-Va in mitochondrial fission

Araujo

Silva-Júnior

Zhang

et al. 2019

Preprint

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“…Mitochondrial morphology is governed by the balance of mitochondrial fusion, mediated by mitofusins and optic atrophy 1 (OPA1), and fission, mediated by dynamin-related protein 1 (Drp1). Disordered mitochondrial dynamics alter metabolism, proliferation, apoptosis and mitophagy, all contributing to serious diseases including neurodegenerative syndromes, pulmonary arterial hypertension (PAH), and cancer [11][12][13][14][15] . Ischaemia may cause vascular dysfunction through Drp1-mediated mitochondrial fission 16 .…”

Section: Introductionmentioning

confidence: 99%

Drp1 regulates mitochondrial dysfunction and dysregulated metabolism in ischemic injury via Clec16a-, BAX-, and GSH- pathways

et al. 2020

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The adaptation of mitochondrial homeostasis to ischemic injury is not fully understood. Here, we studied the role of dynamin-related protein 1 (Drp1) in this process. We found that mitochondrial morphology was altered in the early stage of ischemic injury while mitochondrial dysfunction occurred in the late stage of ischemia. Drp1 appeared to inhibit mitophagy by upregulating mito-Clec16a, which suppressed mito-Parkin recruitment and subsequently impaired the formation of autophagosomes in vascular tissues after ischemic injury. Moreover, ischemia-induced Drp1 activation enhanced apoptosis through inducing mitochondrial translocation of BAX and thereby increasing release of Cytochrome C to activate caspase-3/-9 signalling. Furthermore, Drp1 mediated metabolic disorders and inhibited the levels of mitochondrial glutathione to impair free radical scavenging, leading to further increases in ROS and the exacerbation of mitochondrial dysfunction after ischemic injury. Together, our data suggest a critical role for Drp1 in ischemic injury.

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“…The apparent paradoxical effects of DRP1 in skin wound closure might be explained by different cells or animals, different drugs, different incubation or administration times, different time for measurement, or a combination of these factors in such studies. Moreover, DRP1 also regulated the proliferation of normal human keratinocytes’ proliferation . Moderate mitochondrial fission is essential for growing and dividing cells, in order to populate them with adequate numbers of functioning mitochondria .…”

Section: Discussionmentioning

confidence: 94%

Exogenous hydrogen sulphide supplement accelerates skin wound healing via oxidative stress inhibition and vascular endothelial growth factor enhancement

Hua

et al. 2019

Experimental Dermatology

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Hydrogen sulphide (H2S) is an important gasotransmitter with several physiological functions. However, the roles and the detailed mechanisms of H2S on skin wound healing are not known well. In the present study, 129S1/SvImJ mice were intraperitoneally injected with NaHS (50 μmol/kg/d) for 2 weeks. Then, a round wound of 6 mm diameter with depth into the dermis was made. The skin wound area, blood perfusion, superoxide production, malondialdehyde (MDA) levels, total antioxidant capacity (T‐AOC), expression of vascular endothelial growth factor (VEGF), dynamin‐related protein 1 (DRP1) and optic atrophy 1 (OPA1) were measured. After NaHS (50 μmol/L) pre‐administration for 4 hours, cell migration rate, DRP1, OPA1 and α–smooth muscle actin (α‐SMA) expression, superoxide production and mitochondrial membrane potential in primary skin fibroblasts were measured. Tube formation in human umbilical vein endothelial cells (HUVECs) and cell migration in human keratinocytes were also measured. The results showed that NaHS pretreatment significantly accelerated wound healing and improved blood flow in the wound after operation. NaHS increased VEGF expression in the wound and promoted tube formation in HUVECs. Meanwhile, NaHS attenuated reactive oxygen species (ROS) production, suppressed MDA level but restored T‐AOC in the wound. NaHS also promoted skin fibroblasts migration and α‐SMA expression after scratch. Moreover, NaHS alleviated ROS, increased mitochondrial membrane potential, decreased DRP1 but enhanced OPA1 expression in skin fibroblasts after scratch. NaHS also accelerated human keratinocytes migration after scratch. Taken together, exogenous H2S supplementary accelerated the skin wound healing, which might be related to oxidative stress inhibition and VEGF enhancement.

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Drp1 regulates mitochondrial morphology and cell proliferation in cutaneous squamous cell carcinoma

Abstract: Our results reveal a crucial function for Drp1 in regulating tumor growth, mitochondrial morphology, and cell cycle in cutaneous SCC, suggesting that Drp1 could be a novel target for skin tumor therapies.

Cited by 39 publications

References 28 publications

A novel role for Myosin-Va in mitochondrial fission

A novel role for Myosin-Va in mitochondrial fission

Drp1 regulates mitochondrial dysfunction and dysregulated metabolism in ischemic injury via Clec16a-, BAX-, and GSH- pathways

Exogenous hydrogen sulphide supplement accelerates skin wound healing via oxidative stress inhibition and vascular endothelial growth factor enhancement

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