Interactions between mitoNEET and NAF-1 in cells.
The NEET proteins mitoNEET (mNT) and nutrient-deprivation autophagy factor-1 (NAF-1) are required for cancer cell proliferation and resistance to oxidative stress. NAF-1 and mNT are also implicated in a number of other human pathologies including diabetes, neurodegeneration and cardiovascular diseas...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5398536?pdf=render |
| _version_ | 1828422076131704832 |
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| author | Ola Karmi Sarah H Holt Luhua Song Sagi Tamir Yuting Luo Fang Bai Ammar Adenwalla Merav Darash-Yahana Yang-Sung Sohn Patricia A Jennings Rajeev K Azad Jose' N Onuchic Faruck Morcos Rachel Nechushtai Ron Mittler |
| author_facet | Ola Karmi Sarah H Holt Luhua Song Sagi Tamir Yuting Luo Fang Bai Ammar Adenwalla Merav Darash-Yahana Yang-Sung Sohn Patricia A Jennings Rajeev K Azad Jose' N Onuchic Faruck Morcos Rachel Nechushtai Ron Mittler |
| author_sort | Ola Karmi |
| collection | DOAJ |
| description | The NEET proteins mitoNEET (mNT) and nutrient-deprivation autophagy factor-1 (NAF-1) are required for cancer cell proliferation and resistance to oxidative stress. NAF-1 and mNT are also implicated in a number of other human pathologies including diabetes, neurodegeneration and cardiovascular disease, as well as in development, differentiation and aging. Previous studies suggested that mNT and NAF-1 could function in the same pathway in mammalian cells, preventing the over-accumulation of iron and reactive oxygen species (ROS) in mitochondria. Nevertheless, it is unknown whether these two proteins directly interact in cells, and how they mediate their function. Here we demonstrate, using yeast two-hybrid, in vivo bimolecular fluorescence complementation (BiFC), direct coupling analysis (DCA), RNA-sequencing, ROS and iron imaging, and single and double shRNA lines with suppressed mNT, NAF-1 and mNT/NAF-1 expression, that mNT and NAF-1 directly interact in mammalian cells and could function in the same cellular pathway. We further show using an in vitro cluster transfer assay that mNT can transfer its clusters to NAF-1. Our study highlights the possibility that mNT and NAF-1 function as part of an iron-sulfur (2Fe-2S) cluster relay to maintain the levels of iron and Fe-S clusters under control in the mitochondria of mammalian cells, thereby preventing the activation of apoptosis and/or autophagy and supporting cellular proliferation. |
| first_indexed | 2024-12-10T15:42:24Z |
| format | Article |
| id | doaj.art-b509885fae5a481cb87866730a617cd9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T15:42:24Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b509885fae5a481cb87866730a617cd92022-12-22T01:43:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01124e017579610.1371/journal.pone.0175796Interactions between mitoNEET and NAF-1 in cells.Ola KarmiSarah H HoltLuhua SongSagi TamirYuting LuoFang BaiAmmar AdenwallaMerav Darash-YahanaYang-Sung SohnPatricia A JenningsRajeev K AzadJose' N OnuchicFaruck MorcosRachel NechushtaiRon MittlerThe NEET proteins mitoNEET (mNT) and nutrient-deprivation autophagy factor-1 (NAF-1) are required for cancer cell proliferation and resistance to oxidative stress. NAF-1 and mNT are also implicated in a number of other human pathologies including diabetes, neurodegeneration and cardiovascular disease, as well as in development, differentiation and aging. Previous studies suggested that mNT and NAF-1 could function in the same pathway in mammalian cells, preventing the over-accumulation of iron and reactive oxygen species (ROS) in mitochondria. Nevertheless, it is unknown whether these two proteins directly interact in cells, and how they mediate their function. Here we demonstrate, using yeast two-hybrid, in vivo bimolecular fluorescence complementation (BiFC), direct coupling analysis (DCA), RNA-sequencing, ROS and iron imaging, and single and double shRNA lines with suppressed mNT, NAF-1 and mNT/NAF-1 expression, that mNT and NAF-1 directly interact in mammalian cells and could function in the same cellular pathway. We further show using an in vitro cluster transfer assay that mNT can transfer its clusters to NAF-1. Our study highlights the possibility that mNT and NAF-1 function as part of an iron-sulfur (2Fe-2S) cluster relay to maintain the levels of iron and Fe-S clusters under control in the mitochondria of mammalian cells, thereby preventing the activation of apoptosis and/or autophagy and supporting cellular proliferation.http://europepmc.org/articles/PMC5398536?pdf=render |
| spellingShingle | Ola Karmi Sarah H Holt Luhua Song Sagi Tamir Yuting Luo Fang Bai Ammar Adenwalla Merav Darash-Yahana Yang-Sung Sohn Patricia A Jennings Rajeev K Azad Jose' N Onuchic Faruck Morcos Rachel Nechushtai Ron Mittler Interactions between mitoNEET and NAF-1 in cells. PLoS ONE |
| title | Interactions between mitoNEET and NAF-1 in cells. |
| title_full | Interactions between mitoNEET and NAF-1 in cells. |
| title_fullStr | Interactions between mitoNEET and NAF-1 in cells. |
| title_full_unstemmed | Interactions between mitoNEET and NAF-1 in cells. |
| title_short | Interactions between mitoNEET and NAF-1 in cells. |
| title_sort | interactions between mitoneet and naf 1 in cells |
| url | http://europepmc.org/articles/PMC5398536?pdf=render |
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