Melatonin Represses Mitophagy to Protect Mouse Granulosa Cells from Oxidative Damage
Various environmental stimuli, including oxidative stress, could lead to granulosa cell (GC) death through mitophagy. Recently, it was reported that melatonin (MEL) has a significant effect on GC survival during oxidative damage. Here, we found that MEL inhibited oxidative stress-induced mitophagy t...
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MDPI AG
2021-06-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/11/7/968 |
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| author | Yi Jiang Ming Shen Yuanyuan Chen Yinghui Wei Jingli Tao Honglin Liu |
| author_facet | Yi Jiang Ming Shen Yuanyuan Chen Yinghui Wei Jingli Tao Honglin Liu |
| author_sort | Yi Jiang |
| collection | DOAJ |
| description | Various environmental stimuli, including oxidative stress, could lead to granulosa cell (GC) death through mitophagy. Recently, it was reported that melatonin (MEL) has a significant effect on GC survival during oxidative damage. Here, we found that MEL inhibited oxidative stress-induced mitophagy to promote GC survival. The loss of cell viability upon H<sub>2</sub>O<sub>2</sub> exposure was significantly restored after MEL treatment. Concomitantly, MEL inhibited the activation of mitophagy during oxidative stress. Notably, blocking mitophagy repressed GC death caused by oxidative stress. However, MEL cannot further restore viability of cells treated with mitophagy inhibitor. Moreover, PTEN-induced putative kinase 1 (PINK1), a mitochondrial serine/threonine-protein kinase, was inhibited by MEL during oxidative stress. As a result, the E3 ligase Parkin failed to translocate to mitochondria, leading to impaired mitochondria clearance. Using RNAi to knock down PINK1 expression, we further verified the role of the MEL-PINK1-Parkin (MPP) pathway in maintaining GC survival by suppressing mitophagy. Our findings not only clarify the protective mechanisms of MEL against oxidative damage in GCs, but also extend the understanding about how circadian rhythms might influence follicles development in the ovary. These findings reveal a new mechanism of melatonin in defense against oxidative damage to GCs by repressing mitophagy, which may be a potential therapeutic target for anovulatory disorders. |
| first_indexed | 2024-03-10T09:54:42Z |
| format | Article |
| id | doaj.art-5ab316da2bcc47448ff6a45076b64e7d |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T09:54:42Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-5ab316da2bcc47448ff6a45076b64e7d2023-11-22T02:28:31ZengMDPI AGBiomolecules2218-273X2021-06-0111796810.3390/biom11070968Melatonin Represses Mitophagy to Protect Mouse Granulosa Cells from Oxidative DamageYi Jiang0Ming Shen1Yuanyuan Chen2Yinghui Wei3Jingli Tao4Honglin Liu5College of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaCollege of Animal Science and Technology, Nanjing Agricultural University, Nanjing 210095, ChinaVarious environmental stimuli, including oxidative stress, could lead to granulosa cell (GC) death through mitophagy. Recently, it was reported that melatonin (MEL) has a significant effect on GC survival during oxidative damage. Here, we found that MEL inhibited oxidative stress-induced mitophagy to promote GC survival. The loss of cell viability upon H<sub>2</sub>O<sub>2</sub> exposure was significantly restored after MEL treatment. Concomitantly, MEL inhibited the activation of mitophagy during oxidative stress. Notably, blocking mitophagy repressed GC death caused by oxidative stress. However, MEL cannot further restore viability of cells treated with mitophagy inhibitor. Moreover, PTEN-induced putative kinase 1 (PINK1), a mitochondrial serine/threonine-protein kinase, was inhibited by MEL during oxidative stress. As a result, the E3 ligase Parkin failed to translocate to mitochondria, leading to impaired mitochondria clearance. Using RNAi to knock down PINK1 expression, we further verified the role of the MEL-PINK1-Parkin (MPP) pathway in maintaining GC survival by suppressing mitophagy. Our findings not only clarify the protective mechanisms of MEL against oxidative damage in GCs, but also extend the understanding about how circadian rhythms might influence follicles development in the ovary. These findings reveal a new mechanism of melatonin in defense against oxidative damage to GCs by repressing mitophagy, which may be a potential therapeutic target for anovulatory disorders.https://www.mdpi.com/2218-273X/11/7/968melatoninoxidative damagemitophagygranulosa cellsPINK1-Parkin pathway |
| spellingShingle | Yi Jiang Ming Shen Yuanyuan Chen Yinghui Wei Jingli Tao Honglin Liu Melatonin Represses Mitophagy to Protect Mouse Granulosa Cells from Oxidative Damage Biomolecules melatonin oxidative damage mitophagy granulosa cells PINK1-Parkin pathway |
| title | Melatonin Represses Mitophagy to Protect Mouse Granulosa Cells from Oxidative Damage |
| title_full | Melatonin Represses Mitophagy to Protect Mouse Granulosa Cells from Oxidative Damage |
| title_fullStr | Melatonin Represses Mitophagy to Protect Mouse Granulosa Cells from Oxidative Damage |
| title_full_unstemmed | Melatonin Represses Mitophagy to Protect Mouse Granulosa Cells from Oxidative Damage |
| title_short | Melatonin Represses Mitophagy to Protect Mouse Granulosa Cells from Oxidative Damage |
| title_sort | melatonin represses mitophagy to protect mouse granulosa cells from oxidative damage |
| topic | melatonin oxidative damage mitophagy granulosa cells PINK1-Parkin pathway |
| url | https://www.mdpi.com/2218-273X/11/7/968 |
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