Melatonin attenuates sepsis-induced acute kidney injury by promoting mitophagy through SIRT3-mediated TFAM deacetylation

Zhiya Deng; Man He; Hongbin Hu; Wenqian Zhang; Yaoyuan Zhang; Yue Ge; Tongtong Ma; Jie Wu; Lulan Li; Maomao Sun; Sheng An; Jiaxin Li; Qiaobing Huang; Shenhai Gong; Jiaxing Zhang; Zhongqing Chen; Zhenhua Zeng

doi:10.1080/15548627.2023.2252265

Melatonin attenuates sepsis-induced acute kidney injury by promoting mitophagy through SIRT3-mediated TFAM deacetylation

Autophagy. 2024 Jan;20(1):151-165. doi: 10.1080/15548627.2023.2252265. Epub 2023 Aug 31.

Authors

Zhiya Deng^{1

2}, Man He^{1

2}, Hongbin Hu¹, Wenqian Zhang^{1

2}, Yaoyuan Zhang¹, Yue Ge^{1

3}, Tongtong Ma¹, Jie Wu¹, Lulan Li¹, Maomao Sun^{1

2}, Sheng An^{1

2}, Jiaxin Li¹, Qiaobing Huang^{1

2}, Shenhai Gong^{1

4}, Jiaxing Zhang^{1

5}, Zhongqing Chen¹, Zhenhua Zeng^{1

2}

Affiliations

¹ Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
² Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
³ School of Nursing, Southern Medical University, Guangzhou, Guangdong, China.
⁴ School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
⁵ The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.

Abstract

AKI: acute kidney injury; ATP: adenosine triphosphate; BUN: blood urea nitrogen; CLP: cecal ligation and puncture; eGFR: estimated glomerular filtration rate; H&E: hematoxylin and eosin staining; LCN2/NGAL: lipocalin 2; LPS: lipopolysaccharide; LTL: lotus tetragonolobus lectin; mKeima: mitochondria-targeted Keima; mtDNA: mitochondrial DNA; PAS: periodic acid - Schiff staining; RTECs: renal tubular epithelial cells; SAKI: sepsis-induced acute kidney injury; Scr: serum creatinine; SIRT3: sirtuin 3; TFAM: transcription factor A, mitochondrial; TMRE: tetramethylrhodamine.

Keywords: Acetylation; acute kidney injury; autophagy; critical care; post-translational modification; sepsis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acute Kidney Injury*
Autophagy
DNA, Mitochondrial
DNA-Binding Proteins
Humans
Kidney
Lipopolysaccharides
Melatonin*
Mitochondrial Proteins
Mitophagy
Sepsis* / complications
Sirtuin 3*
Transcription Factors

Substances

Sirtuin 3
Melatonin
Lipopolysaccharides
DNA, Mitochondrial
TFAM protein, human
DNA-Binding Proteins
Transcription Factors
Mitochondrial Proteins
SIRT3 protein, human

Grants and funding

This study was supported by the National Natural Science Foundation of China (grant numbers 82172175, 81871604 and 82002078), the Guangdong Basic and Applied Basic Research Foundation (grant number 2021A1515111028), the Medical Scientific Research Foundation of Guangdong Province of China (grant number A2022120), and the Innovation and entrepreneurship training program for College Students (grant number 202112121241).