Mitochondrially localized MPZL3 emerges as a signaling hub of mammalian physiology

Bioessays. 2021 Oct;43(10):e2100126. doi: 10.1002/bies.202100126. Epub 2021 Sep 6.


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.

Keywords: adipose tissue; circadian clock; epidermal differentiation; hair cycle; mitochondria; sebaceous gland.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CLOCK Proteins
  • Cell Differentiation
  • Circadian Rhythm
  • Hair Follicle*
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Mitochondria* / genetics


  • Membrane Proteins
  • Mpzl3 protein, mouse
  • CLOCK Proteins