SENP1 mediates zinc-induced ZnT6 deSUMOylation at Lys-409 involved in the regulation of zinc metabolism in Golgi apparatus.


Journal

Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402

Informations de publication

Date de publication:
05 Oct 2024
Historique:
received: 01 07 2024
accepted: 16 09 2024
revised: 10 09 2024
medline: 6 10 2024
pubmed: 6 10 2024
entrez: 5 10 2024
Statut: epublish

Résumé

Zinc (Zn) transporters contribute to the maintenance of intracellular Zn homeostasis in vertebrate, whose activity and function are modulated by post-translational modification. However, the function of small ubiquitin-like modifier (SUMOylation) in Zn metabolism remains elusive. Here, compared with low Zn group, a high-Zn diet significantly increases hepatic Zn content and upregulates the expression of metal-response element-binding transcription factor-1 (MTF-1), Zn transporter 6 (ZnT6) and deSUMOylation enzymes (SENP1, SENP2, and SENP6), but inhibits the expression of SUMO proteins and the E1, E2, and E3 enzymes. Mechanistically, Zn triggers the activation of the MTF-1/SENP1 pathway, resulting in the reduction of ZnT6 SUMOylation at Lys 409 by small ubiquitin-like modifier 1 (SUMO1), and promoting the deSUMOylation process mediated by SENP1. SUMOylation modification of ZnT6 has no influence on its localization but reduces its protein stability. Importantly, deSUMOylation of ZnT6 is crucial for controlling Zn export from the cytosols into the Golgi apparatus. In conclusion, for the first time, we elucidate a novel mechanism by which SUMO1-catalyzed SUMOylation and SENP1-mediated deSUMOylation of ZnT6 orchestrate the regulation of Zn metabolism within the Golgi apparatus.

Identifiants

pubmed: 39367979
doi: 10.1007/s00018-024-05452-4
pii: 10.1007/s00018-024-05452-4
doi:

Substances chimiques

Zinc J41CSQ7QDS
Cysteine Endopeptidases EC 3.4.22.-
Cation Transport Proteins 0
Transcription Factor MTF-1 0
Senp1 protein, mouse EC 3.4.22.-
SUMO-1 Protein 0
DNA-Binding Proteins 0
Transcription Factors 0
zinc-binding protein 0
Carrier Proteins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

422

Subventions

Organisme : National Natural Science Foundation of China
ID : 32030111 and 31872585

Informations de copyright

© 2024. The Author(s).

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Auteurs

Chang-Chun Song (CC)

Hubei Hongshan Laboratory, Fishery College, Huazhong Agriculture University, Wuhan, 430070, China.

Tao Liu (T)

Hubei Hongshan Laboratory, Fishery College, Huazhong Agriculture University, Wuhan, 430070, China.

Christer Hogstrand (C)

Diabetes and Nutritional Sciences Division, School of Medicine, King's College London, London, UK.

Chong-Chao Zhong (CC)

Hubei Hongshan Laboratory, Fishery College, Huazhong Agriculture University, Wuhan, 430070, China.

Hua Zheng (H)

Hubei Hongshan Laboratory, Fishery College, Huazhong Agriculture University, Wuhan, 430070, China.

Lv-Hui Sun (LH)

State Key Laboratory of Agricultural Microbiology, Hubei Hongshan Laboratory, Frontiers Science Center for Animal Breeding and Sustainable Production, College of Animal Sciences and Technology, Huazhong Agricultural University, Wuhan, 430070, China.

Zhi Luo (Z)

Hubei Hongshan Laboratory, Fishery College, Huazhong Agriculture University, Wuhan, 430070, China. luozhi99@mail.hzau.edu.cn.
Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266237, China. luozhi99@mail.hzau.edu.cn.

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