The role of TRAP1 in regulating mitochondrial dynamics during acute hypoxia-induced brain injury.
Mitochondrial Dynamics
Animals
Mitochondria
/ metabolism
HSP90 Heat-Shock Proteins
/ metabolism
Brain Injuries
/ metabolism
Neurons
/ metabolism
Humans
Male
Protein Interaction Maps
Molecular Docking Simulation
Mice
Astrocytes
/ metabolism
Mice, Inbred C57BL
Hypoxia
/ complications
Hippocampus
/ metabolism
Acute Disease
Acute hypoxia-induced brain injury
Mechanism
Mitochondrial dynamics
Tumor necrosis factor receptor-associated protein 1 (TRAP1)
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
28 Oct 2024
28 Oct 2024
Historique:
received:
23
07
2024
accepted:
18
10
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
epublish
Résumé
Brain damage caused by acute hypoxia is associated with the physiological activities of mitochondria. Although mitochondria being dynamically regulated, our comprehensive understanding of the response of specific brain cell types to acute hypoxia remains ambiguous. Tumor necrosis factor receptor-associated protein 1 (TRAP1), a mitochondrial-based molecular chaperone, plays a role in controlling mitochondrial movements. Herein, we demonstrated that acute hypoxia significantly alters mitochondria morphology and functionality in both in vivo and in vitro brain injury experiments. Summary-data-based Mendelian Randomization (SMR) analyses revealed possible causative links between mitochondria-related genes and hypoxia injury. Advancing the protein-protein interaction network and molecular docking further elucidated the associations between TRAP1 and mitochondrial dynamics. Furthermore, it was shown that TRAP1 knockdown levels variably affected the expression of key mitochondrial dynamics proteins (DRP1, FIS1, and MFN1/2) in primary hippocampal neurons, astrocytes, and BV-2 cell, leading to changes in mitochondrial structure and function. Understanding the function of TRAP1 in altering mitochondrial physiological activity during hypoxia-induced acute brain injury could help serve as a potential therapeutic target to mitigate neurological damage.
Identifiants
pubmed: 39468583
doi: 10.1186/s12967-024-05780-w
pii: 10.1186/s12967-024-05780-w
doi:
Substances chimiques
HSP90 Heat-Shock Proteins
0
TRAP1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
974Subventions
Organisme : The National Natural Science Foundation of China
ID : 8227051060
Informations de copyright
© 2024. The Author(s).
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