Mono(ADP-ribosyl)ation Enzymes and NAD⁺ Metabolism: A Focus on Diseases and Therapeutic Perspectives

Abstract

Mono(ADP-ribose) transferases and mono(ADP-ribosyl)ating sirtuins use NAD+ to perform the mono(ADP-ribosyl)ation, a simple form of post-translational modification of proteins and, in some cases, of nucleic acids. The availability of NAD+ is a limiting step and an essential requisite for NAD+ consuming enzymes. The synthesis and degradation of NAD+, as well as the transport of its key intermediates among cell compartments, play a vital role in the maintenance of optimal NAD+ levels, which are essential for the regulation of NAD+-utilizing enzymes. In this review, we provide an overview of the current knowledge of NAD+ metabolism, highlighting the functional liaison with mono(ADP-ribosyl)ating enzymes, such as the well-known ARTD10 (also named PARP10), SIRT6, and SIRT7. To this aim, we discuss the link of these enzymes with NAD+ metabolism and chronic diseases, such as cancer, degenerative disorders and aging.

Keywords

• ADP-ribosyl transferase (ADPRT)
• Mono ADP-ribose transferases (mARTs)
• cholera-toxin-like ARTs (ARTCs)
• Diphtheria-toxin-like ARTs (ARTDs)
• Sirtuins (Sirt)
• NAD precursors