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Abstract: FR-PO140

Aldehyde Dehydrogenase 2 Alleviates Mitochondrial Dysfunction by Regulating Aerobic Glycolysis via PI3K/AKT/mTOR Pathway in AKI

Session Information

  • AKI: Mechanisms - II
    November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Li, Jiaying, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
  • Shi, Xiaoxiao, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China
  • Chen, Limeng, Peking Union Medical College Hospital, Dongcheng-qu, Beijing, China

The protective roles of mitochondrial enzyme acetaldehyde dehydrogenase 2 (ALDH2) in various diseases have been reported. In this study, we aimed to investigate the role of ALDH2 on AKI with aerobic glycolysis via the PI3K/AKT/mTOR pathway in different AKI models.


AKI models were established by cisplatin (cis) or maleic acid (MA) intraperitoneally (i.p.) in wild type (WT) and ALDH2 knockout (KO) mice and Alda-1 (ALDH2 agonist) was administrated for prevention experiments. We observed mitochondrial function, aerobic glycolysis, and the PI3K/AKT/mTOR pathway in vivo and in vitro with human renal proximal tubular epithelial (HK-2) cells stimulated by activation or knockdown ALDH2. Furthermore, the rescue experiment was done by LY294002 (inhibitor of PI3K) in HK-2 cells transfected with ALDH2 shRNA (shALDH2) plasmid.


ALDH2 protein was reduced by 46% and 28% in cisplatin and MA induced AKI mice, accompanied by proximal tubular injury and mitochondrial dysfunction. ALDH2 agonist Alda-1 prevented the increase of serum creatinine (Scr) (38.54±4.92 versus 74.42±4.39 μmol/L, P<0.0001) in WT cis-AKI, while more severe (86.13±6.20 versus 62.29±3.19 μmol/L, P<0.01) in ALDH2 KO cis-AKI. In the MA-AKI mice, the renal function (Scr: 20.09±3.65 versus 64.55±12.64 μmol/L, P<0.001) was recovered by Alda-1 pretreatment with reduced KIM-1 protein. In addition, decreased mitochondrial-related proteins (PGC-1α and ATP5a1), mitochondrial DNA (mtDNA) and ATP content were observed in MA-AKI, but reversed by pretreatment with Alda-1. In HK-2 cells, knockdown of ALDH2 aggravated MA-induced mitochondrial dysfunction, indicated by decreased mitochondrial membrane potential and mitochondrial oxygen consumption rate (OCR) (54.80 ± 7.34 versus 40.06 ± 3.58 pmol/min/, P<0.05) with the activation of aerobic glycolysis and PI3K/AKT/mTOR pathway. Furthermore, LY294002 partially reversed the cell apoptosis percentage (15.50%± 0.67 versus 19.50% ± 0.68, P<0.05) of ALDH2 knockdown in MA-induced HK2 cells.


ALDH2 prevented tubular injury and apoptosis by rescuing mitochondrial dysfunction and aerobic glycolysis via the PI3K/AKT/mTOR pathway in cisplatin and MA-induced AKI.