2. Academic Validation
  3. Inhibition of ACSF2 protects against renal ischemia/reperfusion injury via mediating mitophagy in proximal tubular cells

Inhibition of ACSF2 protects against renal ischemia/reperfusion injury via mediating mitophagy in proximal tubular cells

  • Free Radic Biol Med. 2023 Feb 8;S0891-5849(23)00052-7. doi: 10.1016/j.freeradbiomed.2023.02.003.
Haoyu Shi 1,  Hao Qi 1,  Dongdong Xie 1,  Jiayi Zhuang 1,  Huiyue Qi 1,  Yingbo Dai 2,  Jiaqing Wu 3
Affiliations

Affiliations

  • 1 Department of Urology, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China.
  • 2 Department of Urology, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China. Electronic address: [email protected].
  • 3 Department of Urology, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, 519000, China. Electronic address: [email protected].
PMID: 36764625 DOI: 10.1016/j.freeradbiomed.2023.02.003
Abstract

Acute kidney injury (AKI) is a prevalent clinical condition caused by sepsis and ischemia reperfusion (IR) injury. The principal driver of IR-induced AKI involves renal tubular structural changes triggered by the impairment of function in renal tubular cells. The target gene, Acyl-CoA Synthetase Family Member 2 (ACSF2), was retrieved from the GEO database based on high specific expression in renal tubular cells and location in mitochondria. Here, we substantiate that ACSF2 is specifically localized in the mitochondria of the renal tubular epithelium. Functionally silencing ACSF2 in HK2 cells enhanced hypoxia-reoxygenation (HR)-induced Mitophagy, restored mitochondrial function and decreased the production of mitochondrial superoxide. Our study demonstrated that these effects were reversed by silencing Bcl-2 19-kDa interacting protein 3 (BNIP3), a receptor regulating Mitophagy. In vivo, ACSF2 knockdown significantly enhanced IR-induced Mitophagy and improved renal function in mice with IR injury. Conversely, BNIP3 knockdown inhibited Mitophagy and exacerbated renal damage in ACSF2-knockdown mice with IR injury. In conclusion, our study demonstrated that inhibition of ACSF2 enhances Mitophagy, restoring mitochondrial function and protects against IR-induced AKI, providing a new target and potential strategy for therapy.

Keywords

Acute kidney injury; Mitochondria function; Mitophagy; Renal tubular cell.

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