PINK1/Parkin-mediated mitophagy mitigates T-2 toxin-induced nephrotoxicity

Food Chem Toxicol. 2022 Jun:164:113078. doi: 10.1016/j.fct.2022.113078. Epub 2022 Apr 27.

Abstract

T-2 toxin can cause mitochondrial impairment and subsequent renal damage. PINK1/Parkin-mediated mitophagy can mitigate renal impairment by alleviating mitochondrial damage. Nevertheless, the impact of PINK1/Parkin-mediated mitophagy in T-2 toxin-induced renal injury remains unclear. Here, we studied the role of PINK1/Parkin-mediated mitophagy in T-2 toxin-induced nephrotoxicity. Mitochondrial damage was accompanied by NLRP3-inflammasome activation and PINK1/Parkin-mediated mitophagy in the kidney of T-2 toxin-exposed C57BL/6N mice. Knocking out Parkin inhibited the mitophagy but aggravated the structural and functional damage, NLRP3-inflammasome activation, mitochondrial damage, and apoptosis. Correlation analysis revealed that NLRP3-inflammasome activation was correlated with apoptosis. These results show that PINK1/Parkin-mediated mitophagy mitigates T-2 toxin-induced nephrotoxicity.

Keywords: Apoptosis; Mitochondrial injury; Mitophagy; NLRP3-Inflammasome; Nephrotoxicity; T-2 toxin.

MeSH terms

  • Animals
  • Inflammasomes
  • Mice
  • Mice, Inbred C57BL
  • Mitophagy*
  • NLR Family, Pyrin Domain-Containing 3 Protein / genetics
  • Protein Kinases
  • T-2 Toxin* / toxicity
  • Ubiquitin-Protein Ligases / genetics

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Ubiquitin-Protein Ligases
  • Protein Kinases
  • T-2 Toxin