The Yeast-Fermented Garlic and a Balance of Spermine/Spermidine Activates Autophagy via EGR1 Transcriptional Factor

Abstract

Spermine (SPM) and spermidine (SPD) are polyamines found in all organisms, and their concentrations can be regulated by ingestion. We demonstrated that yeast-fermented garlic (YF) extract significantly increased autophag flux in OUMS-36T-1 and HeLa cells expressing the fluorescent probe (GFP-LC3-RFP-LC3ΔG). YF-induced increase of autophagy occurred independently of mTORC1 signaling, and RNA-sequencing analysis revealed that EGR1 was the most significantly altered gene in YF-treated OUMS-36T-1 cells. YF-treated EGR1-deficient HAP1 cells displayed reduced autophagic flux (p < 0.05). YF-induced increasing of autophagic flux occurred via a specific SPM/SPD ratio. HAP1 cells treated with equivalent amounts of SPD or SPM as that found in YF did not increase autophagic flux (p > 0.05); however, treatment with SPD and SPM in the same ratio as that found in YF increased autophagic flux (p < 0.05). This specific SPM/SPD ratio reduced MG132-induced proteostress via EGR1-dependent pathways (p < 0.05). Thus, the SPM/SPD balance may regulate autophagy via EGR1-dependent pathways, and controlling this balance may provide a strategy to maintain cellular homeostasis.