Nanoparticle-Driven Controllable Mitochondrial Regulation through Lysosome–Mitochondria Interactome

Precise subcellular manipulation remains challenging
in quantitative
biological studies. After target modification and hierarchical assembly,
nanoparticles can be functionalized for intracellular investigation.
However, it remains unclear whether nanoparticles themselves can progressively
manipulate subcellular processes, especially organellar networks.
Mitochondria act as the energetic supply, whose fission dynamics are
often modulated by molecular reagents. Here, using different-sized
gold nanoparticles (AuNPs) as a model, we demonstrated the nanoparticle-driven
controllable regulation on mitochondria. Compared with molecular reagents,
AuNPs could induce size-dependent mitochondrial fission without detectable
cell injury, and this process was reversible along with intracellular
AuNPs’ clearance. Mechanistically, it was attributed to the
AuNPs-induced enhanced organelle interactome between lysosomes and
mitochondria. Lysosomal accumulation of AuNPs induced lysosomal swelling
and lysosomal motility alterations, promoting mitochondrial fission
through the increased “kiss” events during the “kiss-and-run”
moving of the lysosome–mitochondria interactome. This study
highlights the fundamental understanding to fully explore the intrinsic
capability of nanoparticles by engineering their basic properties.
Also, it provides practical guidance to investigate the delicate nanolevel
regulation on biological processes.