The Mystery of Extramitochondrial Proteins Lysine Succinylation
Lysine succinylation is a post-translational modification which alters protein function in both physiological and pathological processes. Mindful that it requires succinyl-CoA, a metabolite formed within the mitochondrial matrix that cannot permeate the inner mitochondrial membrane, the question ari...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/11/6085 |
| _version_ | 1797531289291587584 |
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| author | Christos Chinopoulos |
| author_facet | Christos Chinopoulos |
| author_sort | Christos Chinopoulos |
| collection | DOAJ |
| description | Lysine succinylation is a post-translational modification which alters protein function in both physiological and pathological processes. Mindful that it requires succinyl-CoA, a metabolite formed within the mitochondrial matrix that cannot permeate the inner mitochondrial membrane, the question arises as to how there can be succinylation of proteins outside mitochondria. The present mini-review examines pathways participating in peroxisomal fatty acid oxidation that lead to succinyl-CoA production, potentially supporting succinylation of extramitochondrial proteins. Furthermore, the influence of the mitochondrial status on cytosolic NAD<sup>+</sup> availability affecting the activity of cytosolic SIRT5 iso1 and iso4—in turn regulating cytosolic protein lysine succinylations—is presented. Finally, the discovery that glia in the adult human brain lack subunits of both alpha-ketoglutarate dehydrogenase complex and succinate-CoA ligase—thus being unable to produce succinyl-CoA in the matrix—and yet exhibit robust pancellular lysine succinylation, is highlighted. |
| first_indexed | 2024-03-10T10:41:40Z |
| format | Article |
| id | doaj.art-19b5ff5080a54f158ef36379d3e65221 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T10:41:40Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-19b5ff5080a54f158ef36379d3e652212023-11-21T22:51:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012211608510.3390/ijms22116085The Mystery of Extramitochondrial Proteins Lysine SuccinylationChristos Chinopoulos0Department of Biochemistry and Molecular Biology, Semmelweis University, 1094 Budapest, HungaryLysine succinylation is a post-translational modification which alters protein function in both physiological and pathological processes. Mindful that it requires succinyl-CoA, a metabolite formed within the mitochondrial matrix that cannot permeate the inner mitochondrial membrane, the question arises as to how there can be succinylation of proteins outside mitochondria. The present mini-review examines pathways participating in peroxisomal fatty acid oxidation that lead to succinyl-CoA production, potentially supporting succinylation of extramitochondrial proteins. Furthermore, the influence of the mitochondrial status on cytosolic NAD<sup>+</sup> availability affecting the activity of cytosolic SIRT5 iso1 and iso4—in turn regulating cytosolic protein lysine succinylations—is presented. Finally, the discovery that glia in the adult human brain lack subunits of both alpha-ketoglutarate dehydrogenase complex and succinate-CoA ligase—thus being unable to produce succinyl-CoA in the matrix—and yet exhibit robust pancellular lysine succinylation, is highlighted.https://www.mdpi.com/1422-0067/22/11/6085succinyl-CoAketoglutarate dehydrogenase complexpost-translational modificationlysineperoxisomesfatty acid oxidation |
| spellingShingle | Christos Chinopoulos The Mystery of Extramitochondrial Proteins Lysine Succinylation International Journal of Molecular Sciences succinyl-CoA ketoglutarate dehydrogenase complex post-translational modification lysine peroxisomes fatty acid oxidation |
| title | The Mystery of Extramitochondrial Proteins Lysine Succinylation |
| title_full | The Mystery of Extramitochondrial Proteins Lysine Succinylation |
| title_fullStr | The Mystery of Extramitochondrial Proteins Lysine Succinylation |
| title_full_unstemmed | The Mystery of Extramitochondrial Proteins Lysine Succinylation |
| title_short | The Mystery of Extramitochondrial Proteins Lysine Succinylation |
| title_sort | mystery of extramitochondrial proteins lysine succinylation |
| topic | succinyl-CoA ketoglutarate dehydrogenase complex post-translational modification lysine peroxisomes fatty acid oxidation |
| url | https://www.mdpi.com/1422-0067/22/11/6085 |
| work_keys_str_mv | AT christoschinopoulos themysteryofextramitochondrialproteinslysinesuccinylation AT christoschinopoulos mysteryofextramitochondrialproteinslysinesuccinylation |