Latilactobacillus sakei improves resistance to oxidative stress in Caenorhabditis elegans by activating the UPR mt through the HAF-1/ATFS-1 mitochondrial import efficiency regulator

It seems an attractive research direction for microorganisms to show the repair effect on host organisms during host aging. Although previous reports have pointed out the benefits of probiotics in restoring host mitochondrial health, few studies have focused on the important role of mitochondrial unfolded protein response (UPRmt). In this study, we demonstrated that feeding Latilactobacillus sakei ZFM232 (LS232) can enhance the resistance of Caenorhabditis elegans (C. elegans) to different environmental stresses. In addition, we found that LS232 intake increased the cellular respiration rate of nematodes at different stages of aging and effectively prevented mitochondrial aging caused by nematodes as they age. Compared with normal mitochondria, LS232 enhances intestinal mitochondria activity during nematodes' aging process, effectively increasing the mitochondrial membrane potential level at different stages of aging and reducing calcium ion permeability. Through genetic screening, we found that the expression of UPRmt-related genes was significantly upregulated. Then, UPRmt transcriptional activation was demonstrated by mutants' lifespan verification and fluorescent expression of hsp-6 and hsp-60::GFP. In addition, we found that LS232 intake promoted the transfer of the transcription factor ATFS-1 to the nucleus and its expression in the intestine to regulate UPRmt. RNAi interference revealed that the upstream gene haf-1 was also crucial for expressing UPRmt. Finally, we demonstrated that LS232 extends its lifespan by activating UPRmt mainly through HAF-1/ATFS-1 in response to mitochondrial damage repair stress. Our findings elucidate the health benefits of LS232 to the host and its potential application in strategies to improve mitochondrial function.