Neuronal Gtf2i deletion alters mitochondrial and autophagic properties
Abstract Gtf2i encodes the general transcription factor II-I (TFII-I), with peak expression during pre-natal and early post-natal brain development stages. Because these stages are critical for proper brain development, we studied at the single-cell level the consequences of Gtf2i’s deletion from ex...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-12-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05612-5 |
| _version_ | 1797388126463721472 |
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| author | Ariel Nir Sade Gilad Levy Sari Schokoroy Trangle Galit Elad Sfadia Ela Bar Omer Ophir Inbar Fischer May Rokach Andrea Atzmon Hadar Parnas Tali Rosenberg Asaf Marco Orna Elroy Stein Boaz Barak |
| author_facet | Ariel Nir Sade Gilad Levy Sari Schokoroy Trangle Galit Elad Sfadia Ela Bar Omer Ophir Inbar Fischer May Rokach Andrea Atzmon Hadar Parnas Tali Rosenberg Asaf Marco Orna Elroy Stein Boaz Barak |
| author_sort | Ariel Nir Sade |
| collection | DOAJ |
| description | Abstract Gtf2i encodes the general transcription factor II-I (TFII-I), with peak expression during pre-natal and early post-natal brain development stages. Because these stages are critical for proper brain development, we studied at the single-cell level the consequences of Gtf2i’s deletion from excitatory neurons, specifically on mitochondria. Here we show that Gtf2i’s deletion resulted in abnormal morphology, disrupted mRNA related to mitochondrial fission and fusion, and altered autophagy/mitophagy protein expression. These changes align with elevated reactive oxygen species levels, illuminating Gtf2i’s importance in neurons mitochondrial function. Similar mitochondrial issues were demonstrated by Gtf2i heterozygous model, mirroring the human condition in Williams syndrome (WS), and by hemizygous neuronal Gtf2i deletion model, indicating Gtf2i’s dosage-sensitive role in mitochondrial regulation. Clinically relevant, we observed altered transcript levels related to mitochondria, hypoxia, and autophagy in frontal cortex tissue from WS individuals. Our study reveals mitochondrial and autophagy-related deficits shedding light on WS and other Gtf2i-related disorders. |
| first_indexed | 2024-03-08T22:36:20Z |
| format | Article |
| id | doaj.art-4f6a8d1486f84e14ae32d70a925fdfed |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-08T22:36:20Z |
| publishDate | 2023-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-4f6a8d1486f84e14ae32d70a925fdfed2023-12-17T12:27:01ZengNature PortfolioCommunications Biology2399-36422023-12-016111710.1038/s42003-023-05612-5Neuronal Gtf2i deletion alters mitochondrial and autophagic propertiesAriel Nir Sade0Gilad Levy1Sari Schokoroy Trangle2Galit Elad Sfadia3Ela Bar4Omer Ophir5Inbar Fischer6May Rokach7Andrea Atzmon8Hadar Parnas9Tali Rosenberg10Asaf Marco11Orna Elroy Stein12Boaz Barak13The Sagol School of Neuroscience, Tel Aviv UniversityThe Sagol School of Neuroscience, Tel Aviv UniversityThe School of Psychological Sciences, Faculty of Social Sciences, Tel Aviv UniversityThe School of Psychological Sciences, Faculty of Social Sciences, Tel Aviv UniversityThe School of Psychological Sciences, Faculty of Social Sciences, Tel Aviv UniversityThe Sagol School of Neuroscience, Tel Aviv UniversityThe Sagol School of Neuroscience, Tel Aviv UniversityThe Sagol School of Neuroscience, Tel Aviv UniversityThe Shmunis School of Biomedicine & Cancer Research, Faculty of Life Sciences, Tel Aviv UniversityNeuro-Epigenetics Laboratory, Faculty of Agriculture, Food and Environment, The Hebrew University of JerusalemNeuro-Epigenetics Laboratory, Faculty of Agriculture, Food and Environment, The Hebrew University of JerusalemNeuro-Epigenetics Laboratory, Faculty of Agriculture, Food and Environment, The Hebrew University of JerusalemThe Sagol School of Neuroscience, Tel Aviv UniversityThe Sagol School of Neuroscience, Tel Aviv UniversityAbstract Gtf2i encodes the general transcription factor II-I (TFII-I), with peak expression during pre-natal and early post-natal brain development stages. Because these stages are critical for proper brain development, we studied at the single-cell level the consequences of Gtf2i’s deletion from excitatory neurons, specifically on mitochondria. Here we show that Gtf2i’s deletion resulted in abnormal morphology, disrupted mRNA related to mitochondrial fission and fusion, and altered autophagy/mitophagy protein expression. These changes align with elevated reactive oxygen species levels, illuminating Gtf2i’s importance in neurons mitochondrial function. Similar mitochondrial issues were demonstrated by Gtf2i heterozygous model, mirroring the human condition in Williams syndrome (WS), and by hemizygous neuronal Gtf2i deletion model, indicating Gtf2i’s dosage-sensitive role in mitochondrial regulation. Clinically relevant, we observed altered transcript levels related to mitochondria, hypoxia, and autophagy in frontal cortex tissue from WS individuals. Our study reveals mitochondrial and autophagy-related deficits shedding light on WS and other Gtf2i-related disorders.https://doi.org/10.1038/s42003-023-05612-5 |
| spellingShingle | Ariel Nir Sade Gilad Levy Sari Schokoroy Trangle Galit Elad Sfadia Ela Bar Omer Ophir Inbar Fischer May Rokach Andrea Atzmon Hadar Parnas Tali Rosenberg Asaf Marco Orna Elroy Stein Boaz Barak Neuronal Gtf2i deletion alters mitochondrial and autophagic properties Communications Biology |
| title | Neuronal Gtf2i deletion alters mitochondrial and autophagic properties |
| title_full | Neuronal Gtf2i deletion alters mitochondrial and autophagic properties |
| title_fullStr | Neuronal Gtf2i deletion alters mitochondrial and autophagic properties |
| title_full_unstemmed | Neuronal Gtf2i deletion alters mitochondrial and autophagic properties |
| title_short | Neuronal Gtf2i deletion alters mitochondrial and autophagic properties |
| title_sort | neuronal gtf2i deletion alters mitochondrial and autophagic properties |
| url | https://doi.org/10.1038/s42003-023-05612-5 |
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