Mitophagy Promotes Hair Regeneration by Activating Glutathione Metabolism
Dehuan Wang,
Jingwei Jiang,
Mengyue Wang,
Ke Li,
Huan Liang,
Nian’ou Wang,
Weiwei Liu,
Miaomiao Wang,
Siyi Zhou,
Man Zhang,
Yang Xiao,
Xinyu Shen,
Zeming Li,
Wang Wu,
Xia Lin,
Xiao Xiang,
Qiaoli Xie,
Wanqian Liu,
Xun Zhou,
Qu Tang,
Wei Zhou,
Li Yang,
Cheng-Ming Chuong,
Mingxing Lei
Affiliations
Dehuan Wang
Key Laboratory of Biorheological Science and Technology of Ministry of Education and 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering,
Chongqing University, Chongqing 400044, China.
Jingwei Jiang
Key Laboratory of Biorheological Science and Technology of Ministry of Education and 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering,
Chongqing University, Chongqing 400044, China.
Mengyue Wang
Key Laboratory of Biorheological Science and Technology of Ministry of Education and 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering,
Chongqing University, Chongqing 400044, China.
Key Laboratory of Biorheological Science and Technology of Ministry of Education and 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering,
Chongqing University, Chongqing 400044, China.
Miaomiao Wang
Key Laboratory of Biorheological Science and Technology of Ministry of Education and 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering,
Chongqing University, Chongqing 400044, China.
Siyi Zhou
Key Laboratory of Biorheological Science and Technology of Ministry of Education and 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering,
Chongqing University, Chongqing 400044, China.
Man Zhang
Key Laboratory of Biorheological Science and Technology of Ministry of Education and 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering,
Chongqing University, Chongqing 400044, China.
Yang Xiao
Key Laboratory of Biorheological Science and Technology of Ministry of Education and 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering,
Chongqing University, Chongqing 400044, China.
Xinyu Shen
Key Laboratory of Biorheological Science and Technology of Ministry of Education and 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering,
Chongqing University, Chongqing 400044, China.
Zeming Li
Key Laboratory of Biorheological Science and Technology of Ministry of Education and 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering,
Chongqing University, Chongqing 400044, China.
Wang Wu
Key Laboratory of Biorheological Science and Technology of Ministry of Education and 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering,
Chongqing University, Chongqing 400044, China.
Xia Lin
Key Laboratory of Biorheological Science and Technology of Ministry of Education and 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering,
Chongqing University, Chongqing 400044, China.
Xiao Xiang
Key Laboratory of Biorheological Science and Technology of Ministry of Education and 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering,
Chongqing University, Chongqing 400044, China.
Qiaoli Xie
Key Laboratory of Biorheological Science and Technology of Ministry of Education and 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering,
Chongqing University, Chongqing 400044, China.
Wanqian Liu
Key Laboratory of Biorheological Science and Technology of Ministry of Education and 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering,
Chongqing University, Chongqing 400044, China.
Xun Zhou
Department of Dermatology and Cosmetology,
The First Affiliated Hospital of Chongqing College of Traditional Chinese Medicine, Chongqing 400021, China.
Qu Tang
Three Gorges Hospital,
Chongqing University, Chongqing 404000, China.
Wei Zhou
Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment,
Chongqing University Cancer Hospital, Chongqing 400030, China.
Li Yang
Key Laboratory of Biorheological Science and Technology of Ministry of Education and 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering,
Chongqing University, Chongqing 400044, China.
Cheng-Ming Chuong
Department of Pathology, Keck School of Medicine,
University of Southern California, Los Angeles, CA 90033, USA.
Mingxing Lei
Key Laboratory of Biorheological Science and Technology of Ministry of Education and 111 Project Laboratory of Biomechanics and Tissue Repair, College of Bioengineering,
Chongqing University, Chongqing 400044, China.
Mitophagy maintains tissue homeostasis by self-eliminating defective mitochondria through autophagy. How mitophagy regulates stem cell activity during hair regeneration remains unclear. Here, we found that mitophagy promotes the proliferation of hair germ (HG) cells by regulating glutathione (GSH) metabolism. First, single-cell RNA sequencing, mitochondrial probe, transmission electron microscopy, and immunofluorescence staining showed stronger mitochondrial activity and increased mitophagy-related gene especially Prohibitin 2 (Phb2) expression at early-anagen HG compared to the telogen HG. Mitochondrial inner membrane receptor protein PHB2 binds to LC3 to initiate mitophagy. Second, molecular docking and functional studies revealed that PHB2-LC3 activates mitophagy to eliminate the damaged mitochondria in HG. RNA-seq, single-cell metabolism, immunofluorescence staining, and functional validation discovered that LC3 promotes GSH metabolism to supply energy for promoting HG proliferation. Third, transcriptomics analysis and immunofluorescence staining indicated that mitophagy was down-regulated in the aged compared to young-mouse HG. Activating mitophagy and GSH pathways through small-molecule administration can reactivate HG cell proliferation followed by hair regeneration in aged hair follicles. Our findings open up a new avenue for exploring autophagy that promotes hair regeneration and emphasizes the role of the self-elimination effect of mitophagy in controlling the proliferation of HG cells by regulating GSH metabolism.
