Elucidation of ACAT1's role in hepatic ischemia-reperfusion injury: TFEB-mediated mitophagy and ferroptosis modulation as therapeutic targets

Xiangwei Li; Ting Xu; Shaochuang Wang; Long Ma; Xiangyou Yu; Yi Wang; Linlin Bai; Jun Cao; Zuyi Zhao; Meiting Du; Hao Wen; Kun Wu

doi:10.1016/j.jpha.2025.101542

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Xiangwei Li, Ting Xu, Shaochuang Wang, Long Ma, Xiangyou Yu, Yi Wang, Linlin Bai, Jun Cao, Zuyi Zhao, Meiting Du, Hao Wen, Kun Wu. Elucidation of ACAT1's role in hepatic ischemia-reperfusion injury: TFEB-mediated mitophagy and ferroptosis modulation as therapeutic targets[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101542

Citation:

Xiangwei Li, Ting Xu, Shaochuang Wang, Long Ma, Xiangyou Yu, Yi Wang, Linlin Bai, Jun Cao, Zuyi Zhao, Meiting Du, Hao Wen, Kun Wu. Elucidation of ACAT1's role in hepatic ischemia-reperfusion injury: TFEB-mediated mitophagy and ferroptosis modulation as therapeutic targets[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101542

Citation:

Xiangwei Li, Ting Xu, Shaochuang Wang, Long Ma, Xiangyou Yu, Yi Wang, Linlin Bai, Jun Cao, Zuyi Zhao, Meiting Du, Hao Wen, Kun Wu. Elucidation of ACAT1's role in hepatic ischemia-reperfusion injury: TFEB-mediated mitophagy and ferroptosis modulation as therapeutic targets[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101542

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Elucidation of ACAT1's role in hepatic ischemia-reperfusion injury: TFEB-mediated mitophagy and ferroptosis modulation as therapeutic targets

doi: 10.1016/j.jpha.2025.101542

Xiangwei Li¹,
Ting Xu^{2
,
,},
Shaochuang Wang³,
Long Ma⁴,
Xiangyou Yu⁴,
Yi Wang⁴,
Linlin Bai⁵,
Jun Cao^6,7,
Zuyi Zhao⁴,
Meiting Du⁴,
Hao Wen⁶,
Kun Wu^{1
,
,}

1. Department of Gastrointestinal Surgery, The Affiliated Huai’an No.1 People's Hospital of Nanjing Medical University, Huai’an, Jiangsu, 223300, China;
2. Hematology Research Laboratory, The Affiliated Huai’an No.1 People's Hospital of Nanjing Medical University, Huai’an, Jiangsu, 223300, China;
3. Department of Hepatobiliary Surgery, The Affiliated Huai’an No.1 People's Hospital of Nanjing Medical University, Huai’an, Jiangsu, 223300, China;
4. Department of Critical Care Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China;
5. Department of Critical Care Medicine, Shenzhen People's Hospital, Shenzhen, Guangdong, 518020, China;
6. State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, 830054, China;
7. Department of Liver Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China

Funds:

This study was supported by National Natural Science Foundation of China (Grant No.: 82360380),and Huai’an Science and Technology Board Natural science research projects (Grant No.: HAB202304).

Received Date: Apr. 15, 2025
Accepted Date: Dec. 30, 2025
Rev Recd Date: Dec. 29, 2025
Available Online: Jan. 04, 2026

Abstract

Abstract

Hepatic ischemia-reperfusion injury (HIRI) remains a critical clinical challenge, significantly impacting the success of liver transplantation and postoperative recovery following resection. The study investigated the roles of mitochondrial acetyl-CoA acetyltransferase1 (ACAT1) and transcription factor EB (TFEB) in orchestrating cellular responses to HIRI, specifically focusing on mitophagy and ferroptosis pathways. Using a combination of in vivo models and cellular molecular techniques,we found that ACAT1 plays a pivotal hepatoprotective role.By fostering TFEB-mediated mitophagic processes and curtailing ferroptosis, ACAT1 emerges as a critical moderator of cellular resilience against oxidative stresses induced by reperfusion. These findings elucidate the molecular interplay underlying HIRI and identify ACAT1 as a potential therapeutic target for mitigating hepatic damage and enhancing patient outcomes in liver surgery and transplantation scenarios.
- Hepatic ischemia reperfusion injury,
- Single-cell transcriptomics,
- Acetylproteomics,
- Acetyl-CoA acetyltransferase 1,
- Transcription factor EB

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References(50)

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