Inhibition of Mitochondrial Fission Alleviates Zearalenone-Induced Mitochondria-Associated Endoplasmic Reticulum Membrane Dysfunction in Piglet Sertoli Cells

Toxins (Basel). 2023 Mar 30;15(4):253. doi: 10.3390/toxins15040253.

Abstract

This study aimed to investigate the effects of zearalenone (ZEA) on piglet Sertoli cell (SC)-mitochondria-associated endoplasmic reticulum (ER) membranes (MAMs) based on mitochondrial fission, and to explore the molecular mechanism of ZEA-induced cell damage. After the SCs were exposed to the ZEA, the cell viability decreased, the Ca2+ levels increased, and the MAM showed structural damage. Moreover, glucose-regulated protein 75 (Grp75) and mitochondrial Rho-GTPase 1 (Miro1) were upregulated at the mRNA and protein levels. However, phosphofurin acidic cluster protein 2 (PACS2), mitofusin2 (Mfn2), voltage-dependent anion channel 1 (VDAC1), and inositol 1,4,5-trisphosphate receptor (IP3R) were downregulated at the mRNA and protein levels. A pretreatment with mitochondrial division inhibitor 1 (Mdivi-1) decreased the ZEA-induced cytotoxicity toward the SCs. In the ZEA + Mdivi-1 group, the cell viability increased, the Ca2+ levels decreased, the MAM damage was repaired, and the expression levels of Grp75 and Miro1 decreased, while those of PACS2, Mfn2, VDAC1, and IP3R increased compared with those in the ZEA-only group. Thus, ZEA causes MAM dysfunction in piglet SCs through mitochondrial fission, and mitochondria can regulate the ER via MAM.

Keywords: mitochondria-associated endoplasmic-reticulum membrane; mitochondrial fission; piglet Sertoli cells; zearalenone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Endoplasmic Reticulum / metabolism
  • Male
  • Membrane Proteins / metabolism
  • Mitochondria
  • Mitochondrial Dynamics
  • RNA, Messenger / metabolism
  • Sertoli Cells* / metabolism
  • Swine
  • Zearalenone* / metabolism

Substances

  • Zearalenone
  • Membrane Proteins
  • RNA, Messenger
  • Calcium

Grants and funding

This work was funded by the Natural Science Foundation of Anhui Province (grant number 2208085MC81); the Project of Modern Agricultural Industry and Technology System of Anhui Province (grant number AHCYJSTX-05-03); and the College Students Innovation and Entrepreneurship Training Program of Anhui Agricultural University (grant number X202210364415).