Proteolytic rewiring of mitochondria by LONP1 directs cell identity switching of adipocytes
Mitochondrial proteases are emerging as key regulators of mitochondrial plasticity and acting as both protein quality surveillance and regulatory enzymes by performing highly regulated proteolytic reactions. However, it remains unclear whether the regulated mitochondrial proteolysis is mechanistical...
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| Veröffentlicht in: | Nature cell biology 2023-06, Vol.25 (6), p.848-864 |
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| creator | Fu, Tingting Sun, Wanping Xue, Jiachen Zhou, Zheng Wang, Wen Guo, Qiqi Chen, Xinyi Zhou, Danxia Xu, Zhisheng Liu, Lin Xiao, Liwei Mao, Yan Yang, Likun Yin, Yujing Zhang, Xue-Na Wan, Qiangyou Lu, Bin Chen, Yuncong Zhu, Min-Sheng Scherer, Philipp E. Fang, Lei Piao, Hai-Long Shao, Mengle Gan, Zhenji |
| description | Mitochondrial proteases are emerging as key regulators of mitochondrial plasticity and acting as both protein quality surveillance and regulatory enzymes by performing highly regulated proteolytic reactions. However, it remains unclear whether the regulated mitochondrial proteolysis is mechanistically linked to cell identity switching. Here we report that cold-responsive mitochondrial proteolysis is a prerequisite for white-to-beige adipocyte cell fate programming during adipocyte thermogenic remodelling. Thermogenic stimulation selectively promotes mitochondrial proteostasis in mature white adipocytes via the mitochondrial protease LONP1. Disruption of LONP1-dependent proteolysis substantially impairs cold- or β
3
adrenergic agonist-induced white-to-beige identity switching of mature adipocytes. Mechanistically, LONP1 selectively degrades succinate dehydrogenase complex iron sulfur subunit B and ensures adequate intracellular succinate levels. This alters the histone methylation status on thermogenic genes and thereby enables adipocyte cell fate programming. Finally, augmented LONP1 expression raises succinate levels and corrects ageing-related impairments in white-to-beige adipocyte conversion and adipocyte thermogenic capacity. Together, these findings reveal that LONP1 links proteolytic surveillance to mitochondrial metabolic rewiring and directs cell identity conversion during adipocyte thermogenic remodelling.
Fu, Sun, Xue, Zhou et al. show that the mitoprotease LONP1 selectively degrades a complex II component to control intracellular succinate levels, which is needed for white-to-beige adipocyte cell fate programming during adipocyte thermogenic remodelling. |
| doi_str_mv | 10.1038/s41556-023-01155-3 |
| format | Article |
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3
adrenergic agonist-induced white-to-beige identity switching of mature adipocytes. Mechanistically, LONP1 selectively degrades succinate dehydrogenase complex iron sulfur subunit B and ensures adequate intracellular succinate levels. This alters the histone methylation status on thermogenic genes and thereby enables adipocyte cell fate programming. Finally, augmented LONP1 expression raises succinate levels and corrects ageing-related impairments in white-to-beige adipocyte conversion and adipocyte thermogenic capacity. Together, these findings reveal that LONP1 links proteolytic surveillance to mitochondrial metabolic rewiring and directs cell identity conversion during adipocyte thermogenic remodelling.
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adrenergic agonist-induced white-to-beige identity switching of mature adipocytes. Mechanistically, LONP1 selectively degrades succinate dehydrogenase complex iron sulfur subunit B and ensures adequate intracellular succinate levels. This alters the histone methylation status on thermogenic genes and thereby enables adipocyte cell fate programming. Finally, augmented LONP1 expression raises succinate levels and corrects ageing-related impairments in white-to-beige adipocyte conversion and adipocyte thermogenic capacity. Together, these findings reveal that LONP1 links proteolytic surveillance to mitochondrial metabolic rewiring and directs cell identity conversion during adipocyte thermogenic remodelling.
Fu, Sun, Xue, Zhou et al. show that the mitoprotease LONP1 selectively degrades a complex II component to control intracellular succinate levels, which is needed for white-to-beige adipocyte cell fate programming during adipocyte thermogenic remodelling.</description><subject>13</subject><subject>14</subject><subject>38</subject><subject>42</subject><subject>45</subject><subject>631/80</subject><subject>631/80/642/333</subject><subject>64</subject><subject>82</subject><subject>Adipocytes</subject><subject>Adipocytes, Brown - metabolism</subject><subject>Biomedical and Life Sciences</subject><subject>Cancer Research</subject><subject>Cell Biology</subject><subject>Cell fate</subject><subject>Conversion</subject><subject>Developmental Biology</subject><subject>DNA methylation</subject><subject>Histones</subject><subject>Intracellular</subject><subject>Life Sciences</subject><subject>Mitochondria</subject><subject>Mitochondria - metabolism</subject><subject>Mitochondrial Proteins - metabolism</subject><subject>Peptide Hydrolases - 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However, it remains unclear whether the regulated mitochondrial proteolysis is mechanistically linked to cell identity switching. Here we report that cold-responsive mitochondrial proteolysis is a prerequisite for white-to-beige adipocyte cell fate programming during adipocyte thermogenic remodelling. Thermogenic stimulation selectively promotes mitochondrial proteostasis in mature white adipocytes via the mitochondrial protease LONP1. Disruption of LONP1-dependent proteolysis substantially impairs cold- or β
3
adrenergic agonist-induced white-to-beige identity switching of mature adipocytes. Mechanistically, LONP1 selectively degrades succinate dehydrogenase complex iron sulfur subunit B and ensures adequate intracellular succinate levels. This alters the histone methylation status on thermogenic genes and thereby enables adipocyte cell fate programming. Finally, augmented LONP1 expression raises succinate levels and corrects ageing-related impairments in white-to-beige adipocyte conversion and adipocyte thermogenic capacity. Together, these findings reveal that LONP1 links proteolytic surveillance to mitochondrial metabolic rewiring and directs cell identity conversion during adipocyte thermogenic remodelling.
Fu, Sun, Xue, Zhou et al. show that the mitoprotease LONP1 selectively degrades a complex II component to control intracellular succinate levels, which is needed for white-to-beige adipocyte cell fate programming during adipocyte thermogenic remodelling.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>37217599</pmid><doi>10.1038/s41556-023-01155-3</doi><tpages>17</tpages><orcidid>https://orcid.org/0000-0003-0986-8853</orcidid><orcidid>https://orcid.org/0000-0001-7451-0386</orcidid><orcidid>https://orcid.org/0000-0002-2582-4845</orcidid><orcidid>https://orcid.org/0000-0003-3256-6861</orcidid><orcidid>https://orcid.org/0000-0002-8406-4866</orcidid><orcidid>https://orcid.org/0000-0003-0680-3392</orcidid><orcidid>https://orcid.org/0000-0002-5488-9904</orcidid><orcidid>https://orcid.org/0000-0001-5940-207X</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1465-7392 |
| ispartof | Nature cell biology, 2023-06, Vol.25 (6), p.848-864 |
| issn | 1465-7392 1476-4679 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2818053566 |
| source | MEDLINE; Nature; Alma/SFX Local Collection |
| subjects | 13 14 38 42 45 631/80 631/80/642/333 64 82 Adipocytes Adipocytes, Brown - metabolism Biomedical and Life Sciences Cancer Research Cell Biology Cell fate Conversion Developmental Biology DNA methylation Histones Intracellular Life Sciences Mitochondria Mitochondria - metabolism Mitochondrial Proteins - metabolism Peptide Hydrolases - metabolism Programming Proteolysis Stem Cells Succinate dehydrogenase Succinates - metabolism Sulfur Surveillance Switching Sympathomimetics |
| title | Proteolytic rewiring of mitochondria by LONP1 directs cell identity switching of adipocytes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-16T08%3A40%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Proteolytic%20rewiring%20of%20mitochondria%20by%20LONP1%20directs%20cell%20identity%20switching%20of%20adipocytes&rft.jtitle=Nature%20cell%20biology&rft.au=Fu,%20Tingting&rft.date=2023-06-01&rft.volume=25&rft.issue=6&rft.spage=848&rft.epage=864&rft.pages=848-864&rft.issn=1465-7392&rft.eissn=1476-4679&rft_id=info:doi/10.1038/s41556-023-01155-3&rft_dat=%3Cproquest_cross%3E2825596060%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2825596060&rft_id=info:pmid/37217599&rfr_iscdi=true |