Inhibition of the Mitochondrial Pyruvate Carrier Promotes ATF4-Dependent Stress Responsive Metabolic Rewiring and Cell Cycle Arrest in the Human Hair Follicle
TLDR Blocking a key energy pathway in human hair follicles can trigger stress responses that stop cell growth.
The study investigated the role of the Mitochondrial Pyruvate Carrier (MPC) in human hair follicle metabolism, using the MPC1 inhibitor UK5099 on human hair follicles ex vivo. The inhibition of MPC1 resulted in a significant decrease in cell proliferation within the hair follicle epithelium. The researchers found that this inhibition activates ATF4, a transcription factor in the integrated stress response (ISR) pathway, which can halt cell cycle progression. This is linked to the disruption of the TCA cycle and the imbalance of glutathione redox homeostasis. The study also observed an increase in the expression of ATF4 target genes and several transcripts known to regulate cell survival and metabolism. Preliminary data suggests that this response can be mitigated using the ISR inhibitor ISRIB. This research provides the first evidence that human hair follicles can dynamically respond to stress by altering metabolism and upregulating cell survival regulators.
