Nanomaterial- induced mitochondrial biogenesis enhances intercellular mitochondrial transfer efficiency

Intercellular mitochondrial transfer, the spontaneous exchange of mitochondria between cells, is a recently described phenomenon crucial for cellular repair, regeneration, and disease management. Enhancing this natural process holds promise for developing novel therapies targeting diseases associated with mitochondrial dysfunction. Here, we introduce a nanomaterial- based approach employing molybdenum disulfide (MoS2) nanoflowers with atomic- scale vacancies to stimulate mitochondrial biogenesis in cells to make them mitochondrial biofactories. Upon internalization, these nanoflowers result in a two- fold increase in mitochondrial mass and enhancing mitochondrial transfer to recipient cells by several- fold. This enhanced efficiency of transfer significantly improves mitochondrial respiratory capacity and adenosine triphosphate production in recipient cells under physiological conditions. In cellular models of mitochondrial and cellular damage, MoS2 enhanced mitochondrial transfer achieved remarkable restoration of cell function. This proof- of- concept study demonstrates that nanomaterial- boosted intercellular mitochondrial transfer can enhance cell survivability and function under diseased conditions, offering a promising strategy for treating mitochondrial dysfunction- related diseases. Paired-end Illumina RNA-seq of sorted smooth muscle cells (SMCs) alone, after coculture with hMSCs (Mito-Transfer), and after coculture with hMSCs pre-treated with MoS2 nanoflowers.