Mitochondrially localized MPZL3 emerges as a signaling hub of mammalian physiology

Tongyu C. Wikramanayake, Carina Nicu, Jérémy Chéret, Traci A. Czyzyk, Ralf Paus

Research output: Contribution to journalArticlepeer-review


MPZL3 is a nuclear-encoded, mitochondrially localized, immunoglobulin-like V-type protein that functions as a key regulator of epithelial cell differentiation, lipid metabolism, ROS production, glycemic control, and energy expenditure. Recently, MPZL3 has surfaced as an important modulator of sebaceous gland function and of hair follicle cycling, an organ transformation process that is also governed by peripheral clock gene activity and PPARγ. Given the phenotype similarities and differences between Mpzl3 and Pparγ knockout mice, we propose that MPZL3 serves as a signaling hub that is regulated by core clock gene products and/or PPARγ to translate signals from these nuclear transcription factors to the mitochondria to modulate circadian and metabolic regulation. Conservation between murine and human MPZL3 suggests that human MPZL3 may have similarly complex functions in health and disease. We summarize current knowledge and discuss future directions to elucidate the full spectrum of MPZL3 functions in mammalian physiology.

Original languageEnglish (US)
Article number2100126
Issue number10
StatePublished - Oct 2021


  • adipose tissue
  • circadian clock
  • epidermal differentiation
  • hair cycle
  • mitochondria
  • sebaceous gland

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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