Mitophagy associated self-degradation of phosphorylated MAP4 guarantees the migration and proliferation responses of keratinocytes to hypoxia

Feng，Yanhai1,2; Zhang，Qiong3,4; He，Yongqing2; Huang，Yao1,3; Zhang，Junhui5; Zhang，Dongxia3,4; Huang，Yuesheng6; Hu，Jiongyu4,7; Lei，Xia2; Li，Lingfei2

2023-12-01

10.1038/s41420-023-01465-3

Cell Death Discovery   影响因子和分区

2058-7716

Our previous study has announced that phosphorylated microtubule-associated protein 4 (p-MAP4) accelerated keratinocytes migration and proliferation under hypoxia through depolymerizing microtubules. However, p-MAP4 should exhibit inhibitory effects on wound healing, for it also impaired mitochondria. Thus, figuring out the outcome of p-MAP4 after it impaired mitochondria and how the outcome influenced wound healing were far-reaching significance. Herein, the results revealed that p-MAP4 might undergo self-degradation through autophagy in hypoxic keratinocytes. Next, p-MAP4 activated mitophagy which was unobstructed and was also the principal pathway of its self-degradation triggered by hypoxia. Moreover, both Bcl-2 homology 3 (BH3) and LC3 interacting region (LIR) domains had been verified in MAP4, and they endowed MAP4 with the capability to synchronously function as a mitophagy initiator and a mitophagy substrate receptor. And, mutating any one of them ruined hypoxia-induced self-degradation of p-MAP4, resulting in destroyed proliferation and migration responses of keratinocytes to hypoxia. Our findings unviewed that p-MAP4 experienced mitophagy-associated self-degradation through utilizing its BH3 and LIR domains under hypoxia. As a result, the mitophagy-associated self-degradation of p-MAP4 guaranteed the migration and proliferation responses of keratinocytes to hypoxia. Together, this research provided a bran-new pattern of proteins in regulating wound healing, and offered a new direction for intervening wound healing.

SCI

英语

其他

National Natural Science Foundation of China-Yunnan Joint Fund[81773348];Young Scientists Fund[82003323];

WOS:000990290400002

2-s2.0-85159695228

Scopus

1.Army 953 Hospital,Shigatse Branch of Xinqiao Hospital,Third Military Medical University (Army Medical University),Shigatse,China
2.Department of Dermatology,Daping Hospital,Third Military Medical University (Army Medical University),Chongqing,China
3.Institute of Burn Research,Southwest Hospital,Third Military Medical University (Army Medical University),Chongqing,China
4.State Key Laboratory of Trauma,Burns and Combined Injury,Southwest Hospital,Third Military Medical University (Army Medical University),Chongqing,China
5.Department of Geriatric Oncology,Department of Palliative care,Department of Clinical nutrition,Chongqing University Cancer Hospital,Chongqing,China
6.Department of Wound Repair,Institute of Wound Repair and Regeneration Medicine,Southern University of Science and Technology Hospital,Southern University of Science and Technology School of Medicine,Shenzhen,China
7.Endocrinology Department,Southwest Hospital,Third Military Medical University (Army Medical University),Chongqing,China

Feng，Yanhai,Zhang，Qiong,He，Yongqing,et al. Mitophagy associated self-degradation of phosphorylated MAP4 guarantees the migration and proliferation responses of keratinocytes to hypoxia[J]. Cell Death Discovery,2023,9(1).

Feng，Yanhai.,Zhang，Qiong.,He，Yongqing.,Huang，Yao.,Zhang，Junhui.,...&Li，Lingfei.(2023).Mitophagy associated self-degradation of phosphorylated MAP4 guarantees the migration and proliferation responses of keratinocytes to hypoxia.Cell Death Discovery,9(1).

Feng，Yanhai,et al."Mitophagy associated self-degradation of phosphorylated MAP4 guarantees the migration and proliferation responses of keratinocytes to hypoxia".Cell Death Discovery 9.1(2023).