PUBLICATION
Supramolecular Induction of Mitochondrial Aggregation and Fusion
- Authors
- Sun, C., Wang, Z., Yue, L., Huang, Q., Cheng, Q., Wang, R.
- ID
- ZDB-PUB-200828-10
- Date
- 2020
- Source
- Journal of the American Chemical Society 142(39): 16523-16527 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Adamantane/chemistry
- Adamantane/pharmacology*
- Animals
- Cell Line, Tumor
- Cell Survival/drug effects
- Dose-Response Relationship, Drug
- Humans
- Macromolecular Substances/chemistry
- Macromolecular Substances/pharmacology
- Mice
- Mitochondria/drug effects*
- Mitochondria/metabolism
- Molecular Conformation
- Organophosphorus Compounds/chemistry
- Organophosphorus Compounds/pharmacology*
- Polyethylene Glycols/chemistry
- Polyethylene Glycols/pharmacology*
- PubMed
- 32846083 Full text @ J. Am. Chem. Soc.
Citation
Sun, C., Wang, Z., Yue, L., Huang, Q., Cheng, Q., Wang, R. (2020) Supramolecular Induction of Mitochondrial Aggregation and Fusion. Journal of the American Chemical Society. 142(39):16523-16527.
Abstract
Mitochondrial fission is often associated with the development of oxidative stress related diseases, as the fragmentation of mitochondria undermines their membranes, advances production of reactive oxygen species, and promotes apoptosis. Therefore, induction of mitochondrial aggregation and fusion could potentially reverse such medical conditions. Herein, a supramolecular strategy to induce mitochondrial aggregation and fusion is developed for the first time. A polyethylene glycol (PEG) system that was dually tagged with triphenylphosphonium (TPP) and adamantane (ADA), namely TPP-PEG-ADA, was designed to target mitochondria and functionalize their surfaces with ADA. Thereafter, the addition of cucurbit[7]uril (CB[7]) grafted hyaluronic acid (HA) induced supramolecular aggregation and fusion of mitochondria, via strong host-guest interactions between the CB[7] moiety of CB[7]-HA and ADA residing on the surface of mitochondria. As a proof-of-principle, chemically-stressed SH-SY5Y cells and zebrafish neurons were effectively protected via this supramolecular mitochondrial fusion strategy in vitro and in vivo, respectively. This study may open up new venues in not only fundamentally controlling mitochondrial dynamics, but also addressing the medical needs to treat diseases associated with mitochondrial fission and fragmentation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping