We have read with great interest the article by Ye et al. (1), which demonstrates the novel Atg7 regulatory role of 8-oxoguanine-DNA glycosylase (OGG-1), a known DNA repair protein. However, the authors’ claims of interactions between two major cellular events, DNA repair and autophagy, in pulmonary hyperoxia have not been demonstrated well for the following reasons. First, the authors did not check the DNA damage, γ-H2AX, or 8-oxoG in ogg-1 knockout (KO) mice, although they have shown DNA strand breaks in 95% O2–exposed MLE-12 cells that had increased levels of OGG-1. Second, the authors failed to demonstrate that the inflammation in ogg-1 KO mice is merely due to loss of DNA repair. Finally, they showed that p-p65 is upregulated even under normoxic conditions (figures 3A and 6A) in ogg-1 KO mice. Although OGG-1 is implicated in cancer due to its DNA repair role (2), its importance has also been implicated in other pathobiological events, such as diet-induced insulin resistance and airway spasms (3, 4). Interestingly, similar novel roles have been ascribed for various other DNA repair proteins. For example, DNA-PK promotes the Ag presentation potential of dendritic cells (5) and PARP-1 promotes lung inflammation (6, 7). Thus, it is possible that OGG-1 may have multifaceted roles in addition to DNA repair and the authors might have discovered a possible moonlighting role for OGG-1. As evidence to this view, studies have reported that a protective effect of mitochondrially targeted human Ogg-1 is independent of its DNA repair role (8).

Abbreviations used in this article:

KO

knockout

OGG-1

8-oxoguanine-DNA glycosylase.

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