Enhancing TFEB-Mediated Cellular Degradation Pathways by the mTORC1 Inhibitor Quercetin

Area of Science:

• Cellular Biology
• Aging Research
• Neuroscience

Background:

• Mechanistic target of rapamycin (mTOR) signaling is implicated in aging and age-related diseases.
• Transcription factor EB (TFEB) regulates lysosome biogenesis and cellular trafficking, vital for RPE cell function.
• Dysfunctional cellular processes contribute to age-related decline in neuronal tissues.

Purpose of the Study:

• To investigate the effect of quercetin on TFEB activity in retinal pigment epithelium (RPE) cells.
• To determine if quercetin can enhance cellular degradation and self-renewal pathways.
• To explore the potential of quercetin as a therapeutic agent for age-related neuronal conditions.

Main Methods:

• Cultured RPE cells were treated with quercetin.
• TFEB nuclear translocation and transcriptional activity were assessed.
• The impact of quercetin on photoreceptor outer segment degradation was evaluated.
• mTOR and Akt activity were measured.

Main Results:

• Quercetin promoted TFEB nuclear translocation and enhanced its transcriptional activity in RPE cells.
• Activated TFEB facilitated the degradation of phagocytosed photoreceptor outer segments.
• Quercetin directly inhibited mTOR activity without affecting Akt at tested concentrations.
• These findings highlight quercetin's role in activating the TFEB-lysosome axis.

Conclusions:

• Dietary quercetin can improve RPE cell function by enhancing the TFEB-lysosome pathway.
• Quercetin may offer beneficial effects in neuronal tissues by boosting cellular degradation and self-renewal.
• Quercetin shows potential for mitigating age-related cellular dysfunction in the retina and other neuronal tissues.