Figure 1.

NAD⁺ links DNA repair and mitochondrial maintenance. The cellular metabolite NAD⁺ is essential for PARP-dependent generation of poly(ADP-ribose), a process needed to recruit DNA repair proteins at the site of DNA damage sites. NAD⁺ is also a limiting cofactor for SIRTs/sirtuins, such as SIRT1 and the mitochondrial SIRT3. In A-T, persistent PARylation leads to NAD⁺ insufficiency and SIRT1 inactivation, resulting in compromised mitophagy. Other proteins involved in NAD⁺-dependent mitophagy need to be further studied.