Overview of M-LP/MPV17L, a novel atypical PDE and possible target for drug development

Abstract

M-LP/Mpv17L (Mpv17-like protein) was initially identified as a novel protein during screening of age-dependently expressed genes in mouse kidney. Previous findings suggested that human Mpv17-like protein (M-LP/MPV17L) is involved in the maintenance of mitochondrial DNA (mtDNA), thus playing a role in cell defense against mitochondrial dysfunction, although its molecular mechanism of action has remained unknown. Recently, generation of M-LP/MPV17L-knockout (KO) cells using CRISPR-Cas9 technology has revealed that M-LP/MPV17L exerts cyclic nucleotide phosphodiesterase (PDE) activity despite lacking the conserved catalytic region and other structural motifs characteristic of the PDE family, and is one of the key components of pathways such as cAMP/cAMP-dependent protein kinase A (PKA) signaling. Moreover, generation of M-LP/Mpv17L-KO mice has revealed that deficiency of M-LP/Mpv17L results in development of β-cell hyperplasia and improved glucose tolerance, as well as physiological afferent cardiac hypertrophy. M-LP/MPV17L is a protein of great interest as it is a potential target for drug development. Therefore, in this review, we overview the molecular characteristics, regulation of expression, cellular functions, phenotypes detected in KO mice, and disease relevance of M-LP/MPV17L.