Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Department of Organ Transplantation, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Cell Prolif. 2023 Aug;56(8):e13418. doi: 10.1111/cpr.13418. Epub 2023 Feb 14.
Renal ischemia-reperfusion injury (IRI) is mainly responsible for acute kidney injury for which there is no effective therapy. Accumulating evidence has indicated the important role of mitophagy in mitochondrial homeostasis under stress. OGG1 (8-oxoguanine DNA glycosylase) is known for functions in excision repair of nuclear and mitochondrial DNA. However, the role of OGG1 in renal IRI remains unclear. Herein, we identified OGG1, induced during IRI, as a key factor mediating hypoxia-reoxygenation-induced apoptosis in vitro and renal tissue damage in a renal IRI model. We demonstrated that OGG1 expression during IRI negatively regulates mitophagy by suppressing the PINK1/Parkin pathway, thereby aggravating renal ischemic injury. OGG1 knockout and pharmacological inhibition attenuated renal IRI, in part by activating mitophagy. Our results elucidated the damaging role of OGG1 activation in renal IRI, which is associated with the regulatory role of the PINK1/Parkin pathway in mitophagy.
肾缺血再灌注损伤（IRI）主要负责急性肾损伤，目前尚无有效的治疗方法。越来越多的证据表明，自噬在应激下的线粒体动态平衡中起着重要作用。OGG1（8-氧鸟嘌呤 DNA 糖基化酶）已知具有核 DNA 和线粒体 DNA 切除修复的功能。然而，OGG1 在肾 IRI 中的作用尚不清楚。在此，我们鉴定出在 IRI 期间诱导的 OGG1 是一种关键因子，可介导体外缺氧再复氧诱导的细胞凋亡和肾 IRI 模型中的肾组织损伤。我们证明，IRI 期间 OGG1 的表达通过抑制 PINK1/Parkin 通路负调控自噬，从而加重肾缺血损伤。OGG1 敲除和药物抑制部分通过激活自噬减轻肾 IRI。我们的研究结果阐明了 OGG1 激活在肾 IRI 中的损伤作用，这与 PINK1/Parkin 通路在自噬中的调节作用有关。
