Role of diacylglycerol kinase in autophagy, ER biogenesis, and triterpene metabolism
Saccharomyces cerevisiae is widely used for producing various triterpenes by exploiting its native mevalonate/ergosterol pathway. Yeasts that accumulate phospholipids can produce more triterpenes. Our recent study demonstrated that a high phospholipid-accumulating yeast phenotype, as in spt10Δ yeast...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2022-12-01
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| Series: | Autophagy Reports |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/27694127.2022.2105455 |
| _version_ | 1797685705530408960 |
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| author | Kalyani Sai Reju Chaithra Priya S Ravi Manjithaya Venkata Rao Dk |
| author_facet | Kalyani Sai Reju Chaithra Priya S Ravi Manjithaya Venkata Rao Dk |
| author_sort | Kalyani Sai Reju |
| collection | DOAJ |
| description | Saccharomyces cerevisiae is widely used for producing various triterpenes by exploiting its native mevalonate/ergosterol pathway. Yeasts that accumulate phospholipids can produce more triterpenes. Our recent study demonstrated that a high phospholipid-accumulating yeast phenotype, as in spt10Δ yeast, results in increased endoplasmic reticulum (ER) biogenesis, resulting in ER expansion. However, the spt10Δ strain also exhibits high reticulophagy. Dgk1 (diacylglycerol kinase) is an important enzyme in lipid metabolism, which synthesizes phosphatidic acid (PA) by phosphorylating diacylglycerol (DG). We demonstrate that spt10Δ yeast with increased Dgk1 activity offer two desired results, (i) a highly expanded ER, due to redirection of the lipid pathway away from triglycerides towards phospholipid synthesis, increasing ER biogenesis; and (ii) decreased reticulophagy, by increasing the PA pool that activates TOR complex-mediated autophagy suppression. It was speculated that more ER-bound pathway enzymes can fit in the expanded ER, and the mevalonate-ergosterol pathway, being ER bound, might have higher activity. This was demonstrated by the co-expression of Dgk1 and plant triterpene synthase in spt10Δ yeast, which shows a high accumulation of plant triterpene. |
| first_indexed | 2024-03-12T00:55:09Z |
| format | Article |
| id | doaj.art-61590535266542238a90f8d7a96ea9f0 |
| institution | Directory Open Access Journal |
| issn | 2769-4127 |
| language | English |
| last_indexed | 2024-03-12T00:55:09Z |
| publishDate | 2022-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autophagy Reports |
| spelling | doaj.art-61590535266542238a90f8d7a96ea9f02023-09-14T13:24:40ZengTaylor & Francis GroupAutophagy Reports2769-41272022-12-011136837210.1080/27694127.2022.21054552105455Role of diacylglycerol kinase in autophagy, ER biogenesis, and triterpene metabolismKalyani Sai Reju0Chaithra Priya S1Ravi Manjithaya2Venkata Rao Dk3Biochemistry laboratory, CSIR-Central Institute of Medicinal & Aromatic Plants, Research CenterBiochemistry laboratory, CSIR-Central Institute of Medicinal & Aromatic Plants, Research CenterAutophagy lab, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR)Biochemistry laboratory, CSIR-Central Institute of Medicinal & Aromatic Plants, Research CenterSaccharomyces cerevisiae is widely used for producing various triterpenes by exploiting its native mevalonate/ergosterol pathway. Yeasts that accumulate phospholipids can produce more triterpenes. Our recent study demonstrated that a high phospholipid-accumulating yeast phenotype, as in spt10Δ yeast, results in increased endoplasmic reticulum (ER) biogenesis, resulting in ER expansion. However, the spt10Δ strain also exhibits high reticulophagy. Dgk1 (diacylglycerol kinase) is an important enzyme in lipid metabolism, which synthesizes phosphatidic acid (PA) by phosphorylating diacylglycerol (DG). We demonstrate that spt10Δ yeast with increased Dgk1 activity offer two desired results, (i) a highly expanded ER, due to redirection of the lipid pathway away from triglycerides towards phospholipid synthesis, increasing ER biogenesis; and (ii) decreased reticulophagy, by increasing the PA pool that activates TOR complex-mediated autophagy suppression. It was speculated that more ER-bound pathway enzymes can fit in the expanded ER, and the mevalonate-ergosterol pathway, being ER bound, might have higher activity. This was demonstrated by the co-expression of Dgk1 and plant triterpene synthase in spt10Δ yeast, which shows a high accumulation of plant triterpene.http://dx.doi.org/10.1080/27694127.2022.2105455autophagydiacylglycerol kinaseendoplasmic reticulumer stresssynthetic biologytarget of rapamycin (tor) complextriterpene |
| spellingShingle | Kalyani Sai Reju Chaithra Priya S Ravi Manjithaya Venkata Rao Dk Role of diacylglycerol kinase in autophagy, ER biogenesis, and triterpene metabolism Autophagy Reports autophagy diacylglycerol kinase endoplasmic reticulum er stress synthetic biology target of rapamycin (tor) complex triterpene |
| title | Role of diacylglycerol kinase in autophagy, ER biogenesis, and triterpene metabolism |
| title_full | Role of diacylglycerol kinase in autophagy, ER biogenesis, and triterpene metabolism |
| title_fullStr | Role of diacylglycerol kinase in autophagy, ER biogenesis, and triterpene metabolism |
| title_full_unstemmed | Role of diacylglycerol kinase in autophagy, ER biogenesis, and triterpene metabolism |
| title_short | Role of diacylglycerol kinase in autophagy, ER biogenesis, and triterpene metabolism |
| title_sort | role of diacylglycerol kinase in autophagy er biogenesis and triterpene metabolism |
| topic | autophagy diacylglycerol kinase endoplasmic reticulum er stress synthetic biology target of rapamycin (tor) complex triterpene |
| url | http://dx.doi.org/10.1080/27694127.2022.2105455 |
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