Dr. Chun Ju Chang’s group has revealed a crucial link between mitochondrial dynamics and epithelial–mesenchymal transition (EMT), a process implicated in stem-cell-like properties and maintenance. Their study demonstrated that EMT induction in mammary epithelial cells enhances mitochondrial fusion through upregulation of mitofusin 1 (MFN1) and its transcriptional regulator PGC1α, due to the downregulation of the microRNA miR-200c.
This mitochondrial fusion supports asymmetrical cell division and promotes stem cell expansion both in vitro and in vivo. Notably, inhibition of the fission regulator DRP1 mimicked this effect, while MFN1 knockdown prevented it. In mouse models, deletion of Mir-200c triggered Pgc1a–Mfn1 expression, leading to mammary gland hyperplasia with expanded stem cell populations exhibiting increased self-renewal capacity.
Mechanistically, fused mitochondria were preferentially inherited by stem cell progeny during asymmetrical division, a process dependent on MFN1 interaction with the polarity protein PKCζ. This interaction enabled phosphorylation and exclusion of the differentiation factor NUMB from the stem cell progeny. Furthermore, mitochondrial fusion enhanced production of glutathione (GSH), a key antioxidant. Blocking GSH impaired stem cell expansion, while EMT was associated with reduced mitochondrial ROS levels.
Overall, this work highlights mitochondrial fusion as a key regulator of stem cell fate through modulation of polarity cues and oxidative stress. These findings provide valuable insights for developing stem cell–based regenerative therapies and targeting cancer progression. (Cited Source: Nature Reviews Molecular Cell Biology volume 20, page65, 2019)
About Dr. Chun Ju Chang
Dr. Chun Ju Chang is a leading expert in cancer metabolism and epigenetics, currently serving as a full professor at China Medical University in Taiwan. Formerly the dean of the College of Life Sciences, her research has significantly advanced our understanding of breast cancer development and holds promise for novel cancer therapeutic strategies.