Mitochondrially localized MPZL3 emerges as a signaling hub of mammalian physiology

Abstract

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.

Evolution and diversification of Mountain voles (Rodentia: Cricetidae)

“…We identified 127 positively selected genes (PSGs) (Supplementary Data 12 ) using the PAML branch-site model 30 . These genes were associated with physiological processes that may contribute to adaptations such as DNA repair ( RNASEH1 , EYA2 , DEK ) 31 – 33 , eye development (R AB25, WSCD2, MYO7A, MEGF11, RPE65 ), skin and fur ( KRTAP5-1, KRTAP4-6 ), energy production or mitochondrion development ( NDUFS, MPZL3 , TRAK1 , REEP1) 34 , 35 , angiogenesis ( MST1 , PHACTR1, CHRM2 ) 36 , and the somatosensory system 37 ( IGF2BP2 , RHBDF1 ). Furthermore, KEGG and GO enrichment analyses of the PSGs revealed “Retinol metabolism” as a significant process (Supplementary Data 13 , 14 ), which suggested that mountain voles have evolved specific mechanisms to protect their eyes and skins from the risks of UV-induced tumours or other diseases 38 .…”

How and Why the Circadian Clock Regulates Proliferation of Adult Epithelial Stem Cells

“…MPZL3, a nuclear-encoded, mitochondrially localized, immunoglobulin-like V-type protein, has also been proposed as a link between the circadian clock and hair follicle cycling. 35 …”

Targeting mitochondria in dermatological therapy: beyond oxidative damage and skin aging

“…Given that TRH injection has been used for decades as a diagnostic test in thyroid medicine and, thus, has long been licensed for use in patients [190,191], it would not seem impossible to dermatologically repurpose this multifunctional tripeptide neurohormone for clinical use as a novel booster of human epidermal and HF mitochondrial function. Yet, neither mainstream TRH nor translational mitochondrial research have so far pursued this well-supported neuroendocrine "mitochondrial medicine" strategy [40,47,188] In the context of how best to target mitochondrial function in human skin, we are particularly intrigued by a mysterious, mitochondrially localized protein, called Myelin Protein Zero-like 3 (MPZL3) [192,193]. MPZL3 has recently emerged as a key regulator of various aspects of skin differentiation [192], including epidermal morphogenesis and barrier function [80,192,194,195], sebaceous gland differentiation [194,196] and hair follicle cycling [192,197] (Fig.…”

“…Yet, neither mainstream TRH nor translational mitochondrial research have so far pursued this well-supported neuroendocrine "mitochondrial medicine" strategy [40,47,188] In the context of how best to target mitochondrial function in human skin, we are particularly intrigued by a mysterious, mitochondrially localized protein, called Myelin Protein Zero-like 3 (MPZL3) [192,193]. MPZL3 has recently emerged as a key regulator of various aspects of skin differentiation [192], including epidermal morphogenesis and barrier function [80,192,194,195], sebaceous gland differentiation [194,196] and hair follicle cycling [192,197] (Fig. 3).…”