Mitophagy associated self-degradation of phosphorylated MAP4 guarantees the migration and proliferation responses of keratinocytes to hypoxia
Abstract 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 mi...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-05-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-023-01465-3 |
| _version_ | 1827900048074080256 |
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| author | Yanhai Feng Lingfei Li Qiong Zhang Yongqing He Yao Huang Junhui Zhang Dongxia Zhang Yuesheng Huang Xia Lei Jiongyu Hu Gaoxing Luo |
| author_facet | Yanhai Feng Lingfei Li Qiong Zhang Yongqing He Yao Huang Junhui Zhang Dongxia Zhang Yuesheng Huang Xia Lei Jiongyu Hu Gaoxing Luo |
| author_sort | Yanhai Feng |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T23:26:41Z |
| format | Article |
| id | doaj.art-f6e4074dae48438d9ce6b202337987a1 |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-03-12T23:26:41Z |
| publishDate | 2023-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-f6e4074dae48438d9ce6b202337987a12023-07-16T11:09:38ZengNature Publishing GroupCell Death Discovery2058-77162023-05-019111210.1038/s41420-023-01465-3Mitophagy associated self-degradation of phosphorylated MAP4 guarantees the migration and proliferation responses of keratinocytes to hypoxiaYanhai Feng0Lingfei Li1Qiong Zhang2Yongqing He3Yao Huang4Junhui Zhang5Dongxia Zhang6Yuesheng Huang7Xia Lei8Jiongyu Hu9Gaoxing Luo10Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Dermatology, Daping Hospital, Third Military Medical University (Army Medical University)Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Dermatology, Daping Hospital, Third Military Medical University (Army Medical University)Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University)Department of Geriatric Oncology, Department of Palliative care, Department of Clinical nutrition, Chongqing University Cancer HospitalInstitute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University)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 MedicineDepartment of Dermatology, Daping Hospital, Third Military Medical University (Army Medical University)State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University)Institute of Burn Research, Southwest Hospital, Third Military Medical University (Army Medical University)Abstract 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.https://doi.org/10.1038/s41420-023-01465-3 |
| spellingShingle | Yanhai Feng Lingfei Li Qiong Zhang Yongqing He Yao Huang Junhui Zhang Dongxia Zhang Yuesheng Huang Xia Lei Jiongyu Hu Gaoxing Luo Mitophagy associated self-degradation of phosphorylated MAP4 guarantees the migration and proliferation responses of keratinocytes to hypoxia Cell Death Discovery |
| title | Mitophagy associated self-degradation of phosphorylated MAP4 guarantees the migration and proliferation responses of keratinocytes to hypoxia |
| title_full | Mitophagy associated self-degradation of phosphorylated MAP4 guarantees the migration and proliferation responses of keratinocytes to hypoxia |
| title_fullStr | Mitophagy associated self-degradation of phosphorylated MAP4 guarantees the migration and proliferation responses of keratinocytes to hypoxia |
| title_full_unstemmed | Mitophagy associated self-degradation of phosphorylated MAP4 guarantees the migration and proliferation responses of keratinocytes to hypoxia |
| title_short | Mitophagy associated self-degradation of phosphorylated MAP4 guarantees the migration and proliferation responses of keratinocytes to hypoxia |
| title_sort | mitophagy associated self degradation of phosphorylated map4 guarantees the migration and proliferation responses of keratinocytes to hypoxia |
| url | https://doi.org/10.1038/s41420-023-01465-3 |
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