ATP5O Hypo-crotonylation Caused by HDAC2 Hyper-Phosphorylation Is a Primary Detrimental Factor for Downregulated Phospholipid Metabolism under Chronic Stress
Objective. Chronic stress (CS)-induced abnormal metabolism and other subsequent aspects of abnormality are threatening human health. Little is known regarding whether and how protein post-translational-modifications (PTMs) correlate with abnormal metabolism under CS. The aim of this study was to add...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Association for the Advancement of Science (AAAS)
2022-01-01
|
| Series: | Research |
| Online Access: | http://dx.doi.org/10.34133/2022/9834963 |
| _version_ | 1797285821058908160 |
|---|---|
| author | Liang-Jian Chen Zhi-Yuan Tu Yang Wang Yu-Hao He Xin Wang Shu-Zhen Tao Yang-Yang Xu Cong-Rong Li Ruo-Lei Wang Zhi-Xia Yang Jing Sun Xiang Ma Dong Zhang |
| author_facet | Liang-Jian Chen Zhi-Yuan Tu Yang Wang Yu-Hao He Xin Wang Shu-Zhen Tao Yang-Yang Xu Cong-Rong Li Ruo-Lei Wang Zhi-Xia Yang Jing Sun Xiang Ma Dong Zhang |
| author_sort | Liang-Jian Chen |
| collection | DOAJ |
| description | Objective. Chronic stress (CS)-induced abnormal metabolism and other subsequent aspects of abnormality are threatening human health. Little is known regarding whether and how protein post-translational-modifications (PTMs) correlate with abnormal metabolism under CS. The aim of this study was to address this issue and also identify novel key protein PTM. Methods. First, we screened which pan-PTM had significant change between control and CS female mice and whether clinical CS females had similar pan-PTM change. Second, we performed quantitative PTM-omics and metabolomics to verify the correlation between abnormal protein PTMs and atypical metabolism. Third, we performed quantitative phospho-omics to identify the key PTM-regulating enzyme and investigate the interaction between PTM protein and PTM-regulating enzyme. Fourth, we attempted to rectify the abnormal metabolism by correcting the activity of the PTM-regulating enzyme. Finally, we examined whether the selected key protein was also correlated with stress scores and atypical metabolism in clinical women. Results. We initially found that multiple tissues of CS female mice have downregulated pan-crotonylation, and verified that the plasma of clinical CS females also had downregulated pan-crotonylation. Then we determined that ATP5O-K51 crotonylation decreased the most and also caused gross ATP5O decrement, whereas the plasma of CS mice had downregulated phospholipids. Next, downregulating ATP5O crotonylation partially recapitulated the downregulated phospholipid metabolism in CS mice. Next, we verified that HDAC2-S424 phosphorylation determined its decrotonylation activity on ATP5O-K51. Furthermore, correcting HDAC2 hyper-phosphorylation recovered the gross ATP5O level and partially rescued the downregulated phospholipid metabolism in CS mice. Finally, the ATP5O level was also significantly lower and correlated with high stress scores and downregulated phospholipid metabolism in clinical female plasma. Conclusion. This study discovered a novel PTM mechanism involving two distinct types of PTM in CS and provided a novel reference for the clinical precautions and treatments of CS. |
| first_indexed | 2024-03-07T18:08:53Z |
| format | Article |
| id | doaj.art-beba3be5757d48f0bc64e018391f8d6a |
| institution | Directory Open Access Journal |
| issn | 2639-5274 |
| language | English |
| last_indexed | 2024-03-07T18:08:53Z |
| publishDate | 2022-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj.art-beba3be5757d48f0bc64e018391f8d6a2024-03-02T07:51:41ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742022-01-01202210.34133/2022/9834963ATP5O Hypo-crotonylation Caused by HDAC2 Hyper-Phosphorylation Is a Primary Detrimental Factor for Downregulated Phospholipid Metabolism under Chronic StressLiang-Jian Chen0Zhi-Yuan Tu1Yang Wang2Yu-Hao He3Xin Wang4Shu-Zhen Tao5Yang-Yang Xu6Cong-Rong Li7Ruo-Lei Wang8Zhi-Xia Yang9Jing Sun10Xiang Ma11Dong Zhang12State Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166 Jiangsu, China; Department of Obstetrics and Gynecology, Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, ChinaState Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166 Jiangsu, China; State Key Laboratory of Reproductive Medicine, the Center for Clinical Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, ChinaState Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166 Jiangsu, ChinaState Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166 Jiangsu, ChinaState Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166 Jiangsu, ChinaState Key Laboratory of Reproductive Medicine, the Center for Clinical Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, ChinaState Key Laboratory of Reproductive Medicine, the Center for Clinical Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, ChinaState Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166 Jiangsu, ChinaState Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166 Jiangsu, ChinaState Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166 Jiangsu, ChinaDepartment of Psychiatry, Nanjing Brain Hospital affiliated to Nanjing Medical University, Nanjing, 210029 Jiangsu, ChinaState Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166 Jiangsu, ChinaState Key Lab of Reproductive Medicine, Nanjing Medical University, Nanjing, 211166 Jiangsu, China; Animal Core Facility, Nanjing Medical University, Nanjing, 211166, Jiangsu, P .R., ChinaObjective. Chronic stress (CS)-induced abnormal metabolism and other subsequent aspects of abnormality are threatening human health. Little is known regarding whether and how protein post-translational-modifications (PTMs) correlate with abnormal metabolism under CS. The aim of this study was to address this issue and also identify novel key protein PTM. Methods. First, we screened which pan-PTM had significant change between control and CS female mice and whether clinical CS females had similar pan-PTM change. Second, we performed quantitative PTM-omics and metabolomics to verify the correlation between abnormal protein PTMs and atypical metabolism. Third, we performed quantitative phospho-omics to identify the key PTM-regulating enzyme and investigate the interaction between PTM protein and PTM-regulating enzyme. Fourth, we attempted to rectify the abnormal metabolism by correcting the activity of the PTM-regulating enzyme. Finally, we examined whether the selected key protein was also correlated with stress scores and atypical metabolism in clinical women. Results. We initially found that multiple tissues of CS female mice have downregulated pan-crotonylation, and verified that the plasma of clinical CS females also had downregulated pan-crotonylation. Then we determined that ATP5O-K51 crotonylation decreased the most and also caused gross ATP5O decrement, whereas the plasma of CS mice had downregulated phospholipids. Next, downregulating ATP5O crotonylation partially recapitulated the downregulated phospholipid metabolism in CS mice. Next, we verified that HDAC2-S424 phosphorylation determined its decrotonylation activity on ATP5O-K51. Furthermore, correcting HDAC2 hyper-phosphorylation recovered the gross ATP5O level and partially rescued the downregulated phospholipid metabolism in CS mice. Finally, the ATP5O level was also significantly lower and correlated with high stress scores and downregulated phospholipid metabolism in clinical female plasma. Conclusion. This study discovered a novel PTM mechanism involving two distinct types of PTM in CS and provided a novel reference for the clinical precautions and treatments of CS.http://dx.doi.org/10.34133/2022/9834963 |
| spellingShingle | Liang-Jian Chen Zhi-Yuan Tu Yang Wang Yu-Hao He Xin Wang Shu-Zhen Tao Yang-Yang Xu Cong-Rong Li Ruo-Lei Wang Zhi-Xia Yang Jing Sun Xiang Ma Dong Zhang ATP5O Hypo-crotonylation Caused by HDAC2 Hyper-Phosphorylation Is a Primary Detrimental Factor for Downregulated Phospholipid Metabolism under Chronic Stress Research |
| title | ATP5O Hypo-crotonylation Caused by HDAC2 Hyper-Phosphorylation Is a Primary Detrimental Factor for Downregulated Phospholipid Metabolism under Chronic Stress |
| title_full | ATP5O Hypo-crotonylation Caused by HDAC2 Hyper-Phosphorylation Is a Primary Detrimental Factor for Downregulated Phospholipid Metabolism under Chronic Stress |
| title_fullStr | ATP5O Hypo-crotonylation Caused by HDAC2 Hyper-Phosphorylation Is a Primary Detrimental Factor for Downregulated Phospholipid Metabolism under Chronic Stress |
| title_full_unstemmed | ATP5O Hypo-crotonylation Caused by HDAC2 Hyper-Phosphorylation Is a Primary Detrimental Factor for Downregulated Phospholipid Metabolism under Chronic Stress |
| title_short | ATP5O Hypo-crotonylation Caused by HDAC2 Hyper-Phosphorylation Is a Primary Detrimental Factor for Downregulated Phospholipid Metabolism under Chronic Stress |
| title_sort | atp5o hypo crotonylation caused by hdac2 hyper phosphorylation is a primary detrimental factor for downregulated phospholipid metabolism under chronic stress |
| url | http://dx.doi.org/10.34133/2022/9834963 |
| work_keys_str_mv | AT liangjianchen atp5ohypocrotonylationcausedbyhdac2hyperphosphorylationisaprimarydetrimentalfactorfordownregulatedphospholipidmetabolismunderchronicstress AT zhiyuantu atp5ohypocrotonylationcausedbyhdac2hyperphosphorylationisaprimarydetrimentalfactorfordownregulatedphospholipidmetabolismunderchronicstress AT yangwang atp5ohypocrotonylationcausedbyhdac2hyperphosphorylationisaprimarydetrimentalfactorfordownregulatedphospholipidmetabolismunderchronicstress AT yuhaohe atp5ohypocrotonylationcausedbyhdac2hyperphosphorylationisaprimarydetrimentalfactorfordownregulatedphospholipidmetabolismunderchronicstress AT xinwang atp5ohypocrotonylationcausedbyhdac2hyperphosphorylationisaprimarydetrimentalfactorfordownregulatedphospholipidmetabolismunderchronicstress AT shuzhentao atp5ohypocrotonylationcausedbyhdac2hyperphosphorylationisaprimarydetrimentalfactorfordownregulatedphospholipidmetabolismunderchronicstress AT yangyangxu atp5ohypocrotonylationcausedbyhdac2hyperphosphorylationisaprimarydetrimentalfactorfordownregulatedphospholipidmetabolismunderchronicstress AT congrongli atp5ohypocrotonylationcausedbyhdac2hyperphosphorylationisaprimarydetrimentalfactorfordownregulatedphospholipidmetabolismunderchronicstress AT ruoleiwang atp5ohypocrotonylationcausedbyhdac2hyperphosphorylationisaprimarydetrimentalfactorfordownregulatedphospholipidmetabolismunderchronicstress AT zhixiayang atp5ohypocrotonylationcausedbyhdac2hyperphosphorylationisaprimarydetrimentalfactorfordownregulatedphospholipidmetabolismunderchronicstress AT jingsun atp5ohypocrotonylationcausedbyhdac2hyperphosphorylationisaprimarydetrimentalfactorfordownregulatedphospholipidmetabolismunderchronicstress AT xiangma atp5ohypocrotonylationcausedbyhdac2hyperphosphorylationisaprimarydetrimentalfactorfordownregulatedphospholipidmetabolismunderchronicstress AT dongzhang atp5ohypocrotonylationcausedbyhdac2hyperphosphorylationisaprimarydetrimentalfactorfordownregulatedphospholipidmetabolismunderchronicstress |