Tokyo University of Science researchers decode cellular uptake mechanisms for mitochondrial transplantation therapies

Tokyo University of Science researchers identify the endocytic pathways cells use to take up transplanted mitochondria, restoring ATP production and cell health.

By: AXL Media

Published: Mar 4, 2026, 9:26 AM EST

Source: The information in this article was sourced from Tokyo University of Science

The promise of mitochondrial transplantation

Mitochondria are the primary energy producers within the cell, regulating essential functions such as calcium balance, stress responses, and programmed cell death. When these "powerhouses" fail, the resulting energy deficit is a hallmark of neurodegenerative, inflammatory, and metabolic disorders. Mitochondrial transplantation is an emerging therapeutic strategy that involves delivering healthy, isolated mitochondria directly to compromised cells to restore biological stability. While preclinical results have been encouraging, the field has been hampered by a lack of understanding regarding how these organelles interact with recipient cells. Researchers have long questioned whether mitochondria function from outside the cell membrane or if they must be internalized to exert their cytoprotective effects.

Visualizing the internalization process

To address these questions, a research team at the Tokyo University of Science (TUS) focused on mesenchymal stromal cells (MSCs), which are central to regenerative medicine. Using a combination of fluorescence microscopy, flow cytometry, and electron microscopy, the team tracked the movement of isolated mitochondria supplied to living MSCs. The study, published in Scientific Reports, confirmed that mitochondria are internalized by the recipient cells over a period of several hours. Electron microscopy provided definitive proof by revealing mitochondria-like structures encapsulated within membrane-bound vesicles inside the cells, indicating a transition from the extracellular environment to the cell's interior.

Multiple pathways for cellular uptake

The researchers sought to identify the specific biological "doors" that mitochondria use to enter cells. By selectively blocking various entry routes, they discovered that MSCs do not rely on a single mechanism for mitochondrial uptake. Instead, the process involves multiple endocytic pathways, including clathrin-dependent, caveolin-dependent, and actin-dependent mechanisms. This multi-route approach suggests that cells are highly adapted to internalizing these large organelles. Understanding these diverse pathways is a critical step for scientists looking to optimize delivery techniques and tailor transplantation strategies to different types of human tissue.