The Functions of Mitochondrial 2',3'-Cyclic Nucleotide-3'-Phosphodiesterase and Prospects for Its Future.

Krestinina Olga,Baburina Yulia,Papadopoulos Vassilios

doi:10.3390/ijms21093217

Abstract

2′,3′-cyclic nucleotide-3′-phosphodiesterase (CNPase) is a myelin-associated enzyme that catalyzes the phosphodiester hydrolysis of 2’,3’-cyclic nucleotides to 2’-nucleotides. However, its presence is also found in unmyelinated cells and other cellular structures. Understanding of its specific physiological functions, particularly in unmyelinated cells, is still incomplete. This review concentrates on the role of mitochondrial CNPase (mtCNPase), independent of myelin. mtCNPase is able to regulate the functioning of the mitochondrial permeability transition pore (mPTP), and thus is involved in the mechanisms of cell death, both apoptosis and necrosis. Its participation in the development of various diseases and pathological conditions, such as aging, heart disease and alcohol dependence, is also reviewed. As such, mtCNPase can be considered as a potential target for the development of therapeutic strategies in the treatment of mitochondria-related diseases.

Highlights

In the central nervous system of mammals and some vertebrates, a myelin-associated enzyme 2,3 -cyclic nucleotide 3 -phosphodiesterase (CNPase, EC3.1.4.37) is abundantly present
Since we previously showed a relationship between the protective action of MEL on the mitochondria during aging and the decreased levels of mitochondrial mtCNPase with age [88,89], we suggested the presence of a distinctive mechanism for MEL action in mitochondria in relation to pathologies in which mtCNPase may be involved as a key player [90]
The results showed that the levels of mtCNPase increased in rat heart mitochondria (RHM) isolated from rats with acute heart failure, probably to protect them from damage, and that MEL administration strengthened this effect

Summary

Introduction

In the central nervous system of mammals and some vertebrates, a myelin-associated enzyme 2 ,3 -cyclic nucleotide 3 -phosphodiesterase (CNPase, EC3.1.4.37) is abundantly present. Lee and co-authors demonstrated that, due to the mitochondrial targeting signal at the N-terminus, only CNPase was translocated to the mitochondria [14]. This importation was enabled through protein kinase C-mediated phosphorylation of the targeting signal. The diminished levels of CNPase were observed in mitochondria from OLN93 cells with CNPase knockdown that correlated with the facilitated activation of Ca2+ efflux from the mitochondria due to mPTP opening. This process was further stimulated in the presence of 2 ,3 -cAMP [16]. The presence of the phosphorylated form of mtCNPase in mitochondria suggests that mtCNPase might participate in regulatory pathways in mitochondria that rely on phosphorylation [22]

Interaction Partners of mtCNPase

CNPase in Pathology and Aging

Findings

Conclusions