Hypothermic Oxygenated Machine Perfusion Promotes Mitophagy Flux against Hypoxia-Ischemic Injury in Rat DCD Liver
Hypothermic oxygenated machine perfusion (HOPE) can enhance organ preservation and protect mitochondria from hypoxia-ischemic injury; however, an understanding of the underlying HOPE mechanism that protects mitochondria is somewhat lacking. We hypothesized that mitophagy may play an important role i...
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/6/5403 |
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| author | Jia Luo Yiqing Hu Yinbiao Qiao Haoyu Li Jiacheng Huang Kangdi Xu Li Jiang Hao Wu Xiaoyi Hu Junjun Jia Lin Zhou Haiyang Xie Jianhui Li Shusen Zheng |
| author_facet | Jia Luo Yiqing Hu Yinbiao Qiao Haoyu Li Jiacheng Huang Kangdi Xu Li Jiang Hao Wu Xiaoyi Hu Junjun Jia Lin Zhou Haiyang Xie Jianhui Li Shusen Zheng |
| author_sort | Jia Luo |
| collection | DOAJ |
| description | Hypothermic oxygenated machine perfusion (HOPE) can enhance organ preservation and protect mitochondria from hypoxia-ischemic injury; however, an understanding of the underlying HOPE mechanism that protects mitochondria is somewhat lacking. We hypothesized that mitophagy may play an important role in HOPE mitochondria protection. Experimental rat liver grafts were exposed to 30 min of in situ warm ischemia. Then, grafts were procured, followed by cold storage for 3 or 4 h to mimic the conventional preservation and transportation time in donation after circulatory death (DCD) in clinical contexts. Next, the grafts underwent hypothermic machine perfusion (HMP) or HOPE for 1 h through portal vein only perfusion. The HOPE-treated group showed a better preservation capacity compared with cold storage and HMP, preventing hepatocyte damage, nuclear injury, and cell death. HOPE can increase mitophagy marker expression, promote mitophagy flux via the PINK1/Parkin pathway to maintain mitochondrial function, and reduce oxygen free radical generation, while the inhibition of autophagy by 3-methyladenine and chloroquine could reverse the protective effect. HOPE-treated DCD liver also demonstrated more changes in the expression of genes responsible for bile metabolism, mitochondrial dynamics, cell survival, and oxidative stress. Overall, HOPE attenuates hypoxia-ischemic injury in DCD liver by promoting mitophagy flux to maintain mitochondrial function and protect hepatocytes. Mitophagy could pave the way for a protective approach against hypoxia-ischemic injury in DCD liver. |
| first_indexed | 2024-03-11T06:26:15Z |
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| issn | 1661-6596 1422-0067 |
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| last_indexed | 2024-03-11T06:26:15Z |
| publishDate | 2023-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-991a837a9d854a4493a82ea24afbc6ea2023-11-17T11:33:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246540310.3390/ijms24065403Hypothermic Oxygenated Machine Perfusion Promotes Mitophagy Flux against Hypoxia-Ischemic Injury in Rat DCD LiverJia Luo0Yiqing Hu1Yinbiao Qiao2Haoyu Li3Jiacheng Huang4Kangdi Xu5Li Jiang6Hao Wu7Xiaoyi Hu8Junjun Jia9Lin Zhou10Haiyang Xie11Jianhui Li12Shusen Zheng13Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaNHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou 310003, ChinaNHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou 310003, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaNHC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou 310003, ChinaDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, ChinaHypothermic oxygenated machine perfusion (HOPE) can enhance organ preservation and protect mitochondria from hypoxia-ischemic injury; however, an understanding of the underlying HOPE mechanism that protects mitochondria is somewhat lacking. We hypothesized that mitophagy may play an important role in HOPE mitochondria protection. Experimental rat liver grafts were exposed to 30 min of in situ warm ischemia. Then, grafts were procured, followed by cold storage for 3 or 4 h to mimic the conventional preservation and transportation time in donation after circulatory death (DCD) in clinical contexts. Next, the grafts underwent hypothermic machine perfusion (HMP) or HOPE for 1 h through portal vein only perfusion. The HOPE-treated group showed a better preservation capacity compared with cold storage and HMP, preventing hepatocyte damage, nuclear injury, and cell death. HOPE can increase mitophagy marker expression, promote mitophagy flux via the PINK1/Parkin pathway to maintain mitochondrial function, and reduce oxygen free radical generation, while the inhibition of autophagy by 3-methyladenine and chloroquine could reverse the protective effect. HOPE-treated DCD liver also demonstrated more changes in the expression of genes responsible for bile metabolism, mitochondrial dynamics, cell survival, and oxidative stress. Overall, HOPE attenuates hypoxia-ischemic injury in DCD liver by promoting mitophagy flux to maintain mitochondrial function and protect hepatocytes. Mitophagy could pave the way for a protective approach against hypoxia-ischemic injury in DCD liver.https://www.mdpi.com/1422-0067/24/6/5403HOPEDCD livermitophagyhypoxia-ischemic injuryorgan protection |
| spellingShingle | Jia Luo Yiqing Hu Yinbiao Qiao Haoyu Li Jiacheng Huang Kangdi Xu Li Jiang Hao Wu Xiaoyi Hu Junjun Jia Lin Zhou Haiyang Xie Jianhui Li Shusen Zheng Hypothermic Oxygenated Machine Perfusion Promotes Mitophagy Flux against Hypoxia-Ischemic Injury in Rat DCD Liver International Journal of Molecular Sciences HOPE DCD liver mitophagy hypoxia-ischemic injury organ protection |
| title | Hypothermic Oxygenated Machine Perfusion Promotes Mitophagy Flux against Hypoxia-Ischemic Injury in Rat DCD Liver |
| title_full | Hypothermic Oxygenated Machine Perfusion Promotes Mitophagy Flux against Hypoxia-Ischemic Injury in Rat DCD Liver |
| title_fullStr | Hypothermic Oxygenated Machine Perfusion Promotes Mitophagy Flux against Hypoxia-Ischemic Injury in Rat DCD Liver |
| title_full_unstemmed | Hypothermic Oxygenated Machine Perfusion Promotes Mitophagy Flux against Hypoxia-Ischemic Injury in Rat DCD Liver |
| title_short | Hypothermic Oxygenated Machine Perfusion Promotes Mitophagy Flux against Hypoxia-Ischemic Injury in Rat DCD Liver |
| title_sort | hypothermic oxygenated machine perfusion promotes mitophagy flux against hypoxia ischemic injury in rat dcd liver |
| topic | HOPE DCD liver mitophagy hypoxia-ischemic injury organ protection |
| url | https://www.mdpi.com/1422-0067/24/6/5403 |
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