Autophagy inhibitor LRPPRC suppresses mitophagy through interaction with mitophagy initiator Parkin.
Autophagy plays an important role in tumorigenesis. Mitochondrion-associated protein LRPPRC interacts with MAP1S that interacts with LC3 and bridges autophagy components with microtubules and mitochondria to affect autophagy flux. Dysfunction of LRPPRC and MAP1S is associated with poor survival of o...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3983268?pdf=render |
| _version_ | 1818360308793606144 |
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| author | Jing Zou Fei Yue Wenjiao Li Kun Song Xianhan Jiang Jinglin Yi Leyuan Liu |
| author_facet | Jing Zou Fei Yue Wenjiao Li Kun Song Xianhan Jiang Jinglin Yi Leyuan Liu |
| author_sort | Jing Zou |
| collection | DOAJ |
| description | Autophagy plays an important role in tumorigenesis. Mitochondrion-associated protein LRPPRC interacts with MAP1S that interacts with LC3 and bridges autophagy components with microtubules and mitochondria to affect autophagy flux. Dysfunction of LRPPRC and MAP1S is associated with poor survival of ovarian cancer patients. Furthermore, elevated levels of LRPPRC predict shorter overall survival in patients with prostate adenocarcinomas or gastric cancer. To understand the role of LRPPRC in tumor development, previously we reported that LRPPRC forms a ternary complex with Beclin 1 and Bcl-2 to inhibit autophagy. Here we further show that LRPPRC maintains the stability of Parkin that mono-ubiquitinates Bcl-2 to increase Bcl-2 stability to inhibit autophagy. Under mitophagy stress, Parkin translocates to mitochondria to cause rupture of outer mitochondrial membrane and bind with exposed LRPPRC. Consequently, LRPPRC and Parkin help mitochondria being engulfed in autophagosomes to be degraded. In cells under long-term mitophagy stress, both LRPPRC and Parkin become depleted coincident with disappearance of mitochondria and final autophagy inactivation due to depletion of ATG5-ATG12 conjugates. LRPPRC functions as a checkpoint protein that prevents mitochondria from autophagy degradation and impact tumorigenesis. |
| first_indexed | 2024-12-13T20:58:44Z |
| format | Article |
| id | doaj.art-dbf272352ad645cd8ff4867f987a1c69 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T20:58:44Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-dbf272352ad645cd8ff4867f987a1c692022-12-21T23:31:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9490310.1371/journal.pone.0094903Autophagy inhibitor LRPPRC suppresses mitophagy through interaction with mitophagy initiator Parkin.Jing ZouFei YueWenjiao LiKun SongXianhan JiangJinglin YiLeyuan LiuAutophagy plays an important role in tumorigenesis. Mitochondrion-associated protein LRPPRC interacts with MAP1S that interacts with LC3 and bridges autophagy components with microtubules and mitochondria to affect autophagy flux. Dysfunction of LRPPRC and MAP1S is associated with poor survival of ovarian cancer patients. Furthermore, elevated levels of LRPPRC predict shorter overall survival in patients with prostate adenocarcinomas or gastric cancer. To understand the role of LRPPRC in tumor development, previously we reported that LRPPRC forms a ternary complex with Beclin 1 and Bcl-2 to inhibit autophagy. Here we further show that LRPPRC maintains the stability of Parkin that mono-ubiquitinates Bcl-2 to increase Bcl-2 stability to inhibit autophagy. Under mitophagy stress, Parkin translocates to mitochondria to cause rupture of outer mitochondrial membrane and bind with exposed LRPPRC. Consequently, LRPPRC and Parkin help mitochondria being engulfed in autophagosomes to be degraded. In cells under long-term mitophagy stress, both LRPPRC and Parkin become depleted coincident with disappearance of mitochondria and final autophagy inactivation due to depletion of ATG5-ATG12 conjugates. LRPPRC functions as a checkpoint protein that prevents mitochondria from autophagy degradation and impact tumorigenesis.http://europepmc.org/articles/PMC3983268?pdf=render |
| spellingShingle | Jing Zou Fei Yue Wenjiao Li Kun Song Xianhan Jiang Jinglin Yi Leyuan Liu Autophagy inhibitor LRPPRC suppresses mitophagy through interaction with mitophagy initiator Parkin. PLoS ONE |
| title | Autophagy inhibitor LRPPRC suppresses mitophagy through interaction with mitophagy initiator Parkin. |
| title_full | Autophagy inhibitor LRPPRC suppresses mitophagy through interaction with mitophagy initiator Parkin. |
| title_fullStr | Autophagy inhibitor LRPPRC suppresses mitophagy through interaction with mitophagy initiator Parkin. |
| title_full_unstemmed | Autophagy inhibitor LRPPRC suppresses mitophagy through interaction with mitophagy initiator Parkin. |
| title_short | Autophagy inhibitor LRPPRC suppresses mitophagy through interaction with mitophagy initiator Parkin. |
| title_sort | autophagy inhibitor lrpprc suppresses mitophagy through interaction with mitophagy initiator parkin |
| url | http://europepmc.org/articles/PMC3983268?pdf=render |
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