PMID- 36193071 OWN - NLM STAT- MEDLINE DCOM- 20221005 LR - 20221006 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2022 DP - 2022 TI - Mitochondria-Targeted Antioxidant Mitoquinone Maintains Mitochondrial Homeostasis through the Sirt3-Dependent Pathway to Mitigate Oxidative Damage Caused by Renal Ischemia/Reperfusion. PG - 2213503 LID - 10.1155/2022/2213503 [doi] LID - 2213503 AB - Mitochondrial dysfunction is a critical factor contributing to oxidative stress and apoptosis in ischemia-reperfusion (I/R) diseases. Mitoquinone (MitoQ) is a mitochondria-targeted antioxidant whose potent anti-I/R injury capacity has been demonstrated in organs such as the heart and the intestine. In the present study, we explored the role of MitoQ in maintaining mitochondrial homeostasis and attenuating oxidative damage in renal I/R injury. We discovered that the decreased renal function and pathological damage caused by renal I/R injury were significantly ameliorated by MitoQ. MitoQ markedly reversed mitochondrial damage after I/R injury and inhibited renal reactive oxygen species production. In vitro, hypoxia/reoxygenation resulted in increased mitochondrial fission and decreased mitochondrial fusion in human renal tubular epithelial cells (HK-2), which were partially prevented by MitoQ. MitoQ treatment inhibited oxidative stress and reduced apoptosis in HK-2 cells by restoring mitochondrial membrane potential, promoting ATP production, and facilitating mitochondrial fusion. Deeply, renal I/R injury led to a decreased expression of sirtuin-3 (Sirt3), which was recovered by MitoQ. Moreover, the inhibition of Sirt3 partially eliminated the protective effect of MitoQ on mitochondria and increased oxidative damage. Overall, our data demonstrate a mitochondrial protective effect of MitoQ, which raises the possibility of MitoQ as a novel therapy for renal I/R. CI - Copyright (c) 2022 Hu Mao et al. FAU - Mao, Hu AU - Mao H AUID- ORCID: 0000-0003-2252-5572 AD - Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 430060 Hubei, China. FAU - Zhang, Ye AU - Zhang Y AUID- ORCID: 0000-0001-9945-6777 AD - Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 430060 Hubei, China. FAU - Xiong, Yufeng AU - Xiong Y AUID- ORCID: 0000-0001-9810-1691 AD - Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 430060 Hubei, China. FAU - Zhu, Zijing AU - Zhu Z AUID- ORCID: 0000-0003-2615-3040 AD - Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, 430060 Hubei, China. FAU - Wang, Lei AU - Wang L AUID- ORCID: 0000-0001-8412-1130 AD - Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 430060 Hubei, China. FAU - Liu, Xiuheng AU - Liu X AUID- ORCID: 0000-0003-3882-2715 AD - Department of Urology, Renmin Hospital of Wuhan University, Wuhan, 430060 Hubei, China. LA - eng PT - Journal Article DEP - 20220920 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (Antioxidants) RN - 0 (Organophosphorus Compounds) RN - 0 (Reactive Oxygen Species) RN - 1339-63-5 (Ubiquinone) RN - 47BYS17IY0 (mitoquinone) RN - 8L70Q75FXE (Adenosine Triphosphate) RN - EC 3.5.1.- (SIRT3 protein, human) RN - EC 3.5.1.- (Sirtuin 3) SB - IM MH - Adenosine Triphosphate/metabolism MH - Antioxidants/metabolism/pharmacology MH - Homeostasis MH - Humans MH - Ischemia/metabolism MH - *Kidney Diseases/metabolism MH - Mitochondria/metabolism MH - Organophosphorus Compounds/metabolism/pharmacology MH - Oxidative Stress MH - Reactive Oxygen Species/metabolism MH - Reperfusion/adverse effects MH - *Reperfusion Injury/pathology MH - *Sirtuin 3/metabolism MH - Ubiquinone/analogs & derivatives/metabolism/pharmacology PMC - PMC9526615 COIS- The authors declare no conflict of interest. EDAT- 2022/10/05 06:00 MHDA- 2022/10/06 06:00 PMCR- 2022/09/20 CRDT- 2022/10/04 01:54 PHST- 2022/06/24 00:00 [received] PHST- 2022/08/29 00:00 [revised] PHST- 2022/09/01 00:00 [accepted] PHST- 2022/10/04 01:54 [entrez] PHST- 2022/10/05 06:00 [pubmed] PHST- 2022/10/06 06:00 [medline] PHST- 2022/09/20 00:00 [pmc-release] AID - 10.1155/2022/2213503 [doi] PST - epublish SO - Oxid Med Cell Longev. 2022 Sep 20;2022:2213503. doi: 10.1155/2022/2213503. eCollection 2022.