Author interview — Dr. Jyoti Tanwar is an INSPIRE Faculty Fellow working at Regional Centre for Biotechnology (RCB), Faridabad. She has expertise in cellular calcium signaling, focusing on the molecular mechanisms regulating skin pigmentation. She did her Ph.D. from CSIR-Institute of Genomics and Integrative Biology, Delhi in 2022.
Research highlights
- Using primary human melanocytes, mouse cell lines, zebrafish and transgenic mice models; we demonstrate that mitochondrial Ca2+ uniporter (MCU) is an important regulator of pigmentation.
- Our unbiased RNA-sequencing analysis, extensive bioinformatics and robust mechanistic studies identify MCU-NFAT2-Keratin5 signaling axis as a critical determinant of pigmentation.
- Importantly, mitoxantrone, an FDA approved drug that inhibits MCU, reduces pigmentation thereby highlighting therapeutic potential of targeting mitochondrial Ca2+ uptake for clinical management of pigmentary disorders.
Our research shows that mitochondrial calcium uptake plays an important role in regulating skin pigmentation and open new possibilities for treating pigmentary disorders.
Novelty: In this study we reveal the role of mitochondrial Ca2+ uniporter (MCU) complex in regulating vertebrate pigmentation.
Key Findings:
- MCU complex mediated mitochondrial Ca2+ uptake drives vertebrate pigmentation
- Keratin filaments bridge mitochondrial Ca2+ signaling to melanosome biogenesis and maturation
- Transcription factor NFAT2 connects mitochondrial Ca2+ dynamics to keratins expression
- Inhibition of MCU with mitoxantrone, an FDA approved drug, leads to reduction in pigmentation.
“Our findings reveal a critical role of mitochondrial calcium signaling in skin pigmentation. This discovery advances our understanding of pigmentation biology as well as opens up exciting possibilities for novel therapeutic approaches to treat pigment-related disorders.”
– Dr. Rajender K. Motiani
Implications: Our study demonstrates the potential to target mitochondrial calcium signaling for clinical management of pigmentary disorders thereby opening new avenues for treatment strategies.
Reference: Tanwar J, Ahuja K, Sharma A, et al. Mitochondrial calcium uptake orchestrates vertebrate pigmentation via transcriptional regulation of keratin filaments. PLoS Biol. 2024;22(11):e3002895.
