Alopecia is an autoimmune disorder that causes non-scarring hair loss on the scalp and body that is experienced by almost 2% of the global population at some point in their lifetime.

A team of researchers from Australia, Singapore, and China discovered that activated hair follicle stem cells (HFSCs), crucial for hair regrowth and repair, require a powerful protector protein called MCL-1 to function successfully. Without MCL-1, these cells undergo stress and eventually die, leading to hair loss, as reported in a Nature Communications study.

Hair follicles are small tunnel-like structures in the skin where hair grows. These follicles repeatedly cycle through three distinct phases: anagen, the active growth phase; catagen, a transitional phase marked by slowed growth and follicle shrinkage; and telogen, a resting phase where growth ceases and shedding occurs, after which the cycle begins afresh, driven by HFSCs.

Research shows that when HFSCs experience stress from hair shaft loss or follicle shrinkage, they can undergo apoptosis—a controlled way for cells to die— which furthers hair loss. This apoptotic process is controlled by a group of proteins called the BCL-2 family, which decides whether a cell should survive or die.

While it is known that MCL-1, which is part of the BCL-2 family, belongs to the pro-survival protein group, its role in HFSC regulation and hair regeneration is a mystery.

To investigate MCL-1’s influence on HFSC regulation, the researchers of this study deleted the MCL-1 gene from mice skin cells and removed certain patches of existing hair. They found that lack of MCL-1 from birth did not impact the formation of hair follicles but led to gradual hair loss from declining HFSCs over time.

In adult mice, MCL-1 deletion quickly destroyed active HFSCs, which completely stopped hair regeneration in the patches where hair was removed.

The inactive HFSCs remained intact even after MCL-1 deletion, but once they woke up and started dividing to grow new hair, they experienced stress, which triggered the P53 protein essential for regulating cell death. However, deletion of a P53 gene restored hair growth even in the absence of MCL-1, suggesting collaboration between MCL-1 and P53 in maintaining a balance between cell survival and death in hair follicles.

The mice model experiments also revealed that the ERBB signaling pathway (controls cellular processes) plays a key role in keeping active hair follicle stem cells alive by increasing the production of MCL-1.

A deeper knowledge of molecular pathways and interactions that regulate hair follicle growth and cell death paves the way for innovative strategies for treating alopecia and preventing hair loss.

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