Magnetomitotransfer: An efficient way for direct mitochondria transfer into cultured human cells

TLDR

Mitochondrial diseases are largely treated symptomatically, and restoring mitochondrial function remains experimental; transferring healthy mitochondria offers a promising therapeutic avenue, particularly for neurodegenerative disorders. This study introduces magnetomitotransfer, a method that uses anti‑TOM22 magnetic bead‑labeled mitochondria and a magnetic plate to enable efficient mitochondrial transfer for treating mitochondrial pathologies. Mitochondria are labeled with anti‑TOM22 magnetic beads and guided into host cells by a magnetic plate. Magnetomitotransfer achieved 78–92% transfer efficiency versus 0–17% with passive methods, transferred mitochondria rapidly within the first day, and the transferred mitochondria were functional, markedly enhancing cellular respiration.

Abstract

In the course of mitochondrial diseases standard care mostly focuses on treatment of symptoms, while therapeutic approaches aimed at restoring mitochondrial function are currently still in development. The transfer of healthy or modified mitochondria into host cells would open up the possibilities of new cell therapies. Therefore, in this study, a novel method of mitochondrial transfer is proposed by anti-TOM22 magnetic bead-labeled mitochondria with the assistance of a magnetic plate. In comparison to the passive transfer method, the magnetomitotransfer method was more efficient at transferring mitochondria into cells (78-92% vs 0-17% over 3 days). This transfer was also more rapid, with a high ratio of magnetomitotransferred cells and high density of transferred mitochondria within the first day of culture. Importantly, transferred mitochondria appeared to be functional as they strongly enhanced respiration in magnetomitotransferred cells. The novel method of magnetomitotransfer may offer potential for therapeutic approaches for treatment of a variety of mitochondria-associated pathologies, e.g. various neurodegenerative diseases.