The inhibition of TRIM35-mediated TIGAR ubiquitination enhances mitochondrial fusion and alleviates renal ischemia-reperfusion injury

Int J Biol Macromol. 2022 Jun 1;209(Pt A):725-736. doi: 10.1016/j.ijbiomac.2022.04.054. Epub 2022 Apr 12.

Abstract

Tripartite motif 35 (TRIM35) is a member of the tripartite motif protein family and has been recognized to play a key role in immune-inflammatory diseases. However, the role of TRIM35 in renal ischemia-reperfusion injury (IRI) remains unclear. Our study proved that knockdown of TRIM35 alleviates kidney IRI by inhibiting oxidative stress and enhancing mitochondrial fusion. In addition, our experimental results found that TRIM35 interacts with TP53-induced glycolysis and apoptosis regulator (TIGAR) and promotes the polyubiquitination of TIGAR and induces its degradation in the proteasome pathway. Furthermore, TIGAR knockdown significantly inhibited mitochondrial fusion. These results indicate that TRIM35 is a potential therapeutic target for renal IRI.

Keywords: Ischemia-reperfusion injury; Mitochondrial fusion; TIGAR; TRIM35; Ubiquitination.

MeSH terms

  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins* / metabolism
  • Glycolysis
  • Kidney / metabolism
  • Mice
  • Mitochondrial Dynamics*
  • Phosphoric Monoester Hydrolases* / metabolism
  • Reperfusion Injury* / drug therapy
  • Ubiquitination

Substances

  • Apoptosis Regulatory Proteins
  • TRIM35 protein, mouse
  • Phosphoric Monoester Hydrolases
  • TIGAR protein, mouse