Nanoparticle-Driven Controllable Mitochondrial Regulation through Lysosome-Mitochondria Interactome.

Area of Science:

• Cell Biology
• Nanotechnology
• Mitochondrial Dynamics

Background:

• Precise subcellular manipulation is crucial for quantitative biology but remains challenging.
• Nanoparticles are functionalized for intracellular studies, yet their direct manipulation of organellar networks is unclear.
• Mitochondrial fission dynamics are key to cellular energy supply and are modulated by various reagents.

Purpose of the Study:

• To investigate whether nanoparticles can progressively manipulate subcellular processes, specifically organellar networks.
• To demonstrate nanoparticle-driven controllable regulation of mitochondria using gold nanoparticles (AuNPs).
• To elucidate the mechanism underlying nanoparticle-induced mitochondrial regulation.

Main Methods:

• Utilized different-sized gold nanoparticles (AuNPs) as a model system.
• Assessed nanoparticle-induced mitochondrial fission and cell viability.
• Investigated the organelle interactome, focusing on lysosome-mitochondria interactions, and lysosomal dynamics.

Main Results:

• AuNPs induced size-dependent mitochondrial fission, distinct from molecular reagents, without causing detectable cell injury.
• The observed mitochondrial fission was reversible upon intracellular AuNP clearance.
• Mechanistically, AuNPs enhanced the lysosome-mitochondria interactome, leading to lysosomal swelling and altered motility, promoting mitochondrial fission via increased 'kiss' events.

Conclusions:

• Gold nanoparticles can serve as tools for controllable, size-dependent regulation of mitochondrial dynamics.
• Nanoparticle-induced mitochondrial fission is reversible and mediated by altered lysosome-mitochondria interactions.
• This study provides fundamental insights into nanoparticle capabilities and practical guidance for nanolevel biological regulation.