Supramolecular Induction of Mitochondrial Aggregation and Fusion
Chen Sun1, Ziyi Wang1, Ludan Yue1
1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China.
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.
Insights
Researchers developed a novel supramolecular strategy to induce mitochondrial fusion, reversing damage linked to oxidative stress diseases. This approach offers potential therapeutic benefits for conditions involving mitochondrial fragmentation.
Area of Science:
- Biochemistry
- Cell Biology
- Nanotechnology
Background:
- Mitochondrial fission contributes to oxidative stress and apoptosis, driving diseases.
- Reversing mitochondrial fragmentation via aggregation and fusion presents a therapeutic strategy.
Purpose of the Study:
- To develop a novel supramolecular strategy for inducing mitochondrial aggregation and fusion.
- To investigate the potential of this strategy in protecting cells and organisms from mitochondrial damage.
Main Methods:
- Designed a polyethylene glycol (PEG) system dual-tagged with triphenylphosphonium (TPP) and adamantane (ADA) (TPP-PEG-ADA) for mitochondrial targeting.
- Utilized cucurbit[7]uril (CB[7]) grafted hyaluronic acid (HA) to induce supramolecular aggregation via host-guest interactions with ADA on mitochondria.
- Tested the strategy in chemically stressed SH-SY5Y cells (in vitro) and zebrafish neurons (in vivo).
Main Results:
- Successfully induced supramolecular aggregation and fusion of mitochondria using the TPP-PEG-ADA and CB[7]-HA system.
- Demonstrated significant protection of SH-SY5Y cells and zebrafish neurons against chemical stress.
- Validated the efficacy of the supramolecular mitochondrial fusion strategy both in vitro and in vivo.
Conclusions:
- The developed supramolecular strategy effectively induces mitochondrial fusion.
- This approach shows promise for treating diseases associated with mitochondrial fission and fragmentation.
- Opens new avenues for controlling mitochondrial dynamics and developing therapeutic interventions.
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