Related Experiment Video

Updated: Jul 9, 2025

Reverse Genetic Approach to Identify Regulators of Pigmentation using Zebrafish
07:16

Reverse Genetic Approach to Identify Regulators of Pigmentation using Zebrafish

Published on: March 1, 2022

2.3K

The inhibition of VDAC1 oligomerization promotes pigmentation through the CaMK-CRTCs/CREB-MITF pathway

Jinpeng Lv1, Ximei Zhang2, Xiaohong An3

  • 1School of Pharmacy, Changzhou University, Changzhou, 213000, China; Department of Dermatology, The First People's Hospital of Changzhou, The Third Affiliated Hospital of Soochow University, Changzhou, 213000, China.

Experimental Cell Research
|December 9, 2023
PubMed

Insights

Voltage-dependent anion channel 1 (VDAC1) inhibitors promote skin pigmentation by enhancing melanogenesis and melanosome transport. These compounds show potential for treating pigmentation disorders.

Area of Science:

  • Mitochondrial biology
  • Cellular physiology
  • Dermatology

Background:

  • Voltage-dependent anion channel 1 (VDAC1) is crucial for cellular functions and its knockout increases pigment content.
  • Inhibiting VDAC1 oligomerization is a potential therapeutic strategy for various diseases.

Purpose of the Study:

  • To investigate the effect of VDAC1 oligomerization inhibitors on melanogenesis in human epidermal melanocytes (HEMCs).
  • To elucidate the molecular mechanisms underlying VDAC1 inhibitor-induced pigmentation.
  • To evaluate the in vivo efficacy of VDAC1 inhibitors in promoting skin pigmentation.

Main Methods:

  • Treatment of HEMCs with VDAC1 oligomerization inhibitors (VBIT-12, NSC-15364).
  • Analysis of melanogenesis, dendrite formation, and melanosome transport.
  • Investigation of intracellular signaling pathways involving calcium ions, CaMK, CREB, CRTCs, and MITF.
  • In vivo studies in zebrafish and human skin explants.

Main Results:

  • VDAC1 inhibitors promoted melanogenesis, dendrite formation, and melanosome transport in HEMCs.
  • Inhibitors increased intracellular calcium, activated CaMK, leading to CREB phosphorylation and CRTC nuclear translocation.
  • This cascade resulted in increased MITF transcription and subsequent pigmentation.
  • In vivo studies confirmed increased pigmentation in zebrafish and human skin explants.

Conclusions:

  • VDAC1 oligomerization inhibitors effectively promote skin pigmentation through a calcium-dependent signaling pathway.
  • These findings highlight the therapeutic potential of VDAC1 inhibitors for treating skin pigmentation disorders.
Keywords:
CaMK–CRTCs/CREB–MITF pathwayMelanogenesisMelanosome transportPigmentation disordersVDAC1 oligomerization

More Related Videos

Quantification of Hypopigmentation Activity In Vitro06:08

Quantification of Hypopigmentation Activity In Vitro

Published on: March 6, 2019

11.3K
Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model12:37

Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model

Published on: September 7, 2013

18.3K

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.6K
Photoreceptors and Visual Pathways01:22

Photoreceptors and Visual Pathways

At the molecular level, visual signals trigger transformations in photopigment molecules, resulting in changes in the photoreceptor cell's membrane potential. The photon's energy level is denoted by its wavelength, with each specific wavelength of visible light associated with a distinct color. The spectral range of visible light, classified as electromagnetic radiation, spans from 380 to 720 nm. Electromagnetic radiation wavelengths exceeding 720 nm fall under the infrared category,...
6.0K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.6K