Role of Ubiquilins for Brown Adipocyte Proteostasis and Thermogenesis
The acclimatization of brown adipose tissue (BAT) to sustained cold exposure requires an adaptive increase in proteasomal protein quality control. Ubiquilins represent a recently identified family of shuttle proteins with versatile functions in protein degradation, such as facilitating substrate tar...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2021.739021/full |
| _version_ | 1823934993194287104 |
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| author | Carolin Muley Stefan Kotschi Alexander Bartelt Alexander Bartelt Alexander Bartelt Alexander Bartelt |
| author_facet | Carolin Muley Stefan Kotschi Alexander Bartelt Alexander Bartelt Alexander Bartelt Alexander Bartelt |
| author_sort | Carolin Muley |
| collection | DOAJ |
| description | The acclimatization of brown adipose tissue (BAT) to sustained cold exposure requires an adaptive increase in proteasomal protein quality control. Ubiquilins represent a recently identified family of shuttle proteins with versatile functions in protein degradation, such as facilitating substrate targeting and proteasomal degradation. However, whether ubiquilins participate in brown adipocyte function has not been investigated so far. Here, we determine the role of ubiquilins for proteostasis and non-shivering thermogenesis in brown adipocytes. We found that Ubqln1, 2 and 4 are highly expressed in BAT and their expression was induced by cold and proteasomal inhibition. Surprisingly, silencing of ubiquilin gene expression (one or multiple in combinations) did not lead to aggravated ER stress or inflammation. Moreover, ubiquitin level and proteasomal activity under basal conditions were not impacted by loss of ubiquilins. Also, non-shivering thermogenesis measured by norepinephrine-induced respiration remained intact after loss of ubiquilins. In conclusion, ubiquilin proteins are highly abundant in BAT and regulated by cold, but they are dispensable for brown adipocyte proteostasis and thermogenesis. |
| first_indexed | 2024-12-16T22:28:45Z |
| format | Article |
| id | doaj.art-27008e2fdd854d329b8150205ba89a43 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-16T22:28:45Z |
| publishDate | 2021-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-27008e2fdd854d329b8150205ba89a432022-12-21T22:13:47ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-09-011210.3389/fendo.2021.739021739021Role of Ubiquilins for Brown Adipocyte Proteostasis and ThermogenesisCarolin Muley0Stefan Kotschi1Alexander Bartelt2Alexander Bartelt3Alexander Bartelt4Alexander Bartelt5Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University, Munich, GermanyInstitute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University, Munich, GermanyInstitute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians-University, Munich, GermanyGerman Center for Cardiovascular Research, Partner Site Munich Heart Alliance, Technische Universität München, Munich, GermanyInstitute for Diabetes and Cancer (IDC), Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, GermanyDepartment of Molecular Metabolism & Sabri Ülker Center, Harvard T.H. Chan School of Public Health, Boston, MA, United StatesThe acclimatization of brown adipose tissue (BAT) to sustained cold exposure requires an adaptive increase in proteasomal protein quality control. Ubiquilins represent a recently identified family of shuttle proteins with versatile functions in protein degradation, such as facilitating substrate targeting and proteasomal degradation. However, whether ubiquilins participate in brown adipocyte function has not been investigated so far. Here, we determine the role of ubiquilins for proteostasis and non-shivering thermogenesis in brown adipocytes. We found that Ubqln1, 2 and 4 are highly expressed in BAT and their expression was induced by cold and proteasomal inhibition. Surprisingly, silencing of ubiquilin gene expression (one or multiple in combinations) did not lead to aggravated ER stress or inflammation. Moreover, ubiquitin level and proteasomal activity under basal conditions were not impacted by loss of ubiquilins. Also, non-shivering thermogenesis measured by norepinephrine-induced respiration remained intact after loss of ubiquilins. In conclusion, ubiquilin proteins are highly abundant in BAT and regulated by cold, but they are dispensable for brown adipocyte proteostasis and thermogenesis.https://www.frontiersin.org/articles/10.3389/fendo.2021.739021/fullubiquilinsbrown adipose tissuecold adaptationthermogenesisproteostasisubiquitin-proteasome-system |
| spellingShingle | Carolin Muley Stefan Kotschi Alexander Bartelt Alexander Bartelt Alexander Bartelt Alexander Bartelt Role of Ubiquilins for Brown Adipocyte Proteostasis and Thermogenesis Frontiers in Endocrinology ubiquilins brown adipose tissue cold adaptation thermogenesis proteostasis ubiquitin-proteasome-system |
| title | Role of Ubiquilins for Brown Adipocyte Proteostasis and Thermogenesis |
| title_full | Role of Ubiquilins for Brown Adipocyte Proteostasis and Thermogenesis |
| title_fullStr | Role of Ubiquilins for Brown Adipocyte Proteostasis and Thermogenesis |
| title_full_unstemmed | Role of Ubiquilins for Brown Adipocyte Proteostasis and Thermogenesis |
| title_short | Role of Ubiquilins for Brown Adipocyte Proteostasis and Thermogenesis |
| title_sort | role of ubiquilins for brown adipocyte proteostasis and thermogenesis |
| topic | ubiquilins brown adipose tissue cold adaptation thermogenesis proteostasis ubiquitin-proteasome-system |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2021.739021/full |
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