biostudies-literaturePeng YNational Natural Science Foundation of ChinaNational Natural Science Foundation of China (National Science Foundation of China)1078https://www.ebi.ac.uk/biostudies/studies/S-EPMC12852848biostudies-literatureUnknown17(1)Inspired by the non-transmembrane transfer of mitochondria in cell-to-cell communications, herein, we report an original exploration to accelerate mitochondrial intercellular transport, and its application to exogenous cargo delivery. We discover that deliberate PINK1-targeted mitophagy downregulation elevates mitochondrial transit capacity via multifaceted drivers-morphological adaptation, metabolic reprogramming, and respiratory enhancement. Capitalizing on this, we engineer high-speed mitochondrial vehicles for photosensitizer hitchhiking, with spatiotemporal tracking elucidating its dynamic intercellular transit and physiological impacts. Through mitochondria's communication network-tunneling nanotubes (TNTs), the mitochondria-photosensitizer cotransporter achieves reinforced intercellNature communicationsLeveraging engineered mitochondria through intercellular communication network for accelerated transport and delivery.PMC1285284882373806Peng YLi XYang ZYang YLi JQi XDu YZhou YLin MGao DfalseLeveraging engineered mitochondria through intercellular communication network for accelerated transport and delivery.Inspired by the non-transmembrane transfer of mitochondria in cell-to-cell communications, herein, we report an original exploration to accelerate mitochondrial intercellular transport, and its application to exogenous cargo delivery. We discover that deliberate PINK1-targeted mitophagy downregulation elevates mitochondrial transit capacity via multifaceted drivers-morphological adaptation, metabolic reprogramming, and respiratory enhancement. Capitalizing on this, we engineer high-speed mitochondrial vehicles for photosensitizer hitchhiking, with spatiotemporal tracking elucidating its dynamic intercellular transit and physiological impacts. Through mitochondria's communication network-tunneling nanotubes (TNTs), the mitochondria-photosensitizer cotransporter achieves reinforced intercell2025-01-01T00:00:00Z2025 Dec2026-06-16T07:18:10.94Z2026-06-16T03:10:10.611ZS-EPMC128528484143647410.1038/s41467-025-67837-8