Serpina3k lactylation protects from cardiac ischemia reperfusion injury

Lactate produced during ischemia-reperfusion injury is known to promote lactylation of proteins, which play controversial roles. By analyzing the lactylomes and proteomes of mouse myocardium during ischemia-reperfusion injury using mass spectrometry, we show that both Serpina3k protein expression and its lactylation at lysine 351 are increased upon reperfusion. Both Serpina3k and its human homolog, SERPINA3, are abundantly expressed in cardiac fibroblasts, but not in cardiomyocytes. Biochemically, lactylation of Serpina3k enhances protein stability. Using Serpina3k knockout mice and mice overexpressing its lactylation-deficient mutant, we find that Serpina3k protects from cardiac injury in a lysine 351…

• NN
  National Natural Science Foundation of China

  Awards: 82088101, -I2M-2-003, 82070287
• CA
  Chinese Academy of Medical Sciences

  Awards: 2022-I2M-2-001, 2022-
• FH
  Fuwai Hospital, Chinese Academy of Medical Sciences
• CA
  Chinese Academy of Medical Sciences Initiative for Innovative Medicine

  Awards: 2021-1-I2M-006, 2022-I2M-2-001