Mitochondrially localized MPZL3 emerges as a signaling hub of mammalian physiology

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 PPAR gamma. Given the phenotype similarities and differences between Mpzl3 and Ppar gamma knockout mice, we propose that MPZL3 serves as a signaling hub that is regulated by core clock gene products and/or PPAR gamma 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.

Automated summary

MPZL3 is a crucial regulator of various physiological processes such as sebaceous gland function and hair follicle cycling, potentially influenced by core clock gene activity and PPAR gamma. The conservation between murine and human MPZL3 suggests complex functions in health and disease, with potential for further research to fully understand its role in mammalian physiology.