MPC1 promotes the damage of human coronary endothelial cells in macrolide-resistant mycoplasma pneumoniae via inhibiting mitophagy

Introduction Mycoplasma pneumoniae ( M. pneumoniae ) is a common community-acquired pneumonias among children and young adults. Long-term use of macrolide antibiotics treatment contributes to Macrolide-resistant M. pneumoniae (MRMP). This study aimed to investigate the roles of mitochondrial pyruvate carrier 1 (MPC1) in MRMP. Methods Human coronary endothelial cells (HCAECs) were co-cultured with MRMP. mRNA expression was calculated using quantitative reverse transcriptase PCR (qRT-PCR). Protein expression was detected using Western blot. Cytokine release was detected using enzyme-linked immunosorbent assay. The morphology of mitochondria was detected using transmission electron microscopy assay. The viability of HCAECs was determined using cell counting kit-8 assay. Cytotoxicity was determined using lactate dehydrogenase cytotoxicity assay. Cell death was analyzed using terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay. Results We found that MRMP exposure mediated mitochondrial damage and pyroptosis of HCAECs. Moreover, MPC1 was overexpressed in HCAECs exposed to MRMP. Inhibition of MPC1 promoted mitophagy as well as suppressed the pyroptosis of HCAECs. However, blocking mitophagy signaling antagonized the effects of MPC1 deficiency, resulting in mitochondrial damage and pyroptosis of HCAECs. Conclusion MPC1 promotes mitochondrial damage and pyroptosis of HCAECs in MRMP through inhibiting mitophagy. Therefore, targeting MPC1 may be a promising strategy for MRMP.