A Guide for Studying Mitochondria Transfer, 2023, Tiash et al

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A Guide for Studying Mitochondria Transfer

Tiash S, Brestoff JR, Crewe C.

Abstract
Mitochondria can shuttle between adjacent cells or travel to distant organs by breaking away from the parent cell and entering circulation. Here, we briefly review the state of the mitochondria transfer field and discuss a methodological framework for studying mitochondria transfer.

It has been almost 20 years since the discovery that organelles can be shuttled between cells in proximity via tube-like structures called tunneling nanotubes (TNTs). The first report of mitochondria transfer was suggested to occur through TNTs, although the mechanism was not fully elucidated. Mitochondria can be transferred through cell contact-dependent processes such as TNTs, transient cellular fusion, or gap junction internalization (Figure 1). The latter is a process by which connexin-mediated gap junctions connecting two cells are internalized by one cell, resulting in engulfment of cellular material from the second cell.

Furthermore, mitochondria can also be transferred through cell contact-independent processes, where mitochondria are shed into the extracellular space and then taken up by other cells within the tissue or enter the circulation for delivery to cells in distant organs. This comment focuses on the methodological considerations for the rigorous study of mitochondria transfer.


Link (Nat Cell Biol.)
https://doi.org/10.1038/s41556-023-01246-1

 

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A couple of useful quotes

Cell contact-dependent mechanisms of mitochondria transfer involve separating intact mitochondria from the parent mitochondrial network and delivering them to the recipient cell. In contrast, transfer mechanisms involving extracellular mitochondria are more heterogenous. Intact mitochondria and/or mitochondria-derived vesicles (MDVs) can be released from cells either as naked mitochondria/MDVs or enclosed in a membrane bilayer derived from the endolysosomal system or plasma membrane.

Several methods have been used to track the intercellular movement of mitochondria: tracking mitochondria stained with mitochondrial dyes, following sequence variants in mitochondrial DNA (mtDNA), or tracking mitochondria labeled with genetically encoded fluorescent proteins or tags.

One limitation of all methods is that they cannot always distinguish between the transfer of intact mitochondria and the uptake of debris from dying cells

A second limitation is that fragments of mitochondria, such as MDVs, may not contain the molecule used to track mitochondria transfer. Therefore, care should be used in the interpretation of mitochondria transfer data.

And in closing they say this

As this field matures, we are tasked with developing tools to manipulate the ability of cells to transfer mitochondria and robustly track mitochondria in vivo. As most mitochondria transfer studies have been conducted in cells or mice, there is no definitive evidence of mitochondria transfer in humans, which is hindering the deployment of therapeutic strategies based on mitochondria transfer. However, it is interesting to note that healthy human blood contains significant numbers of mitochondria, suggesting a role in the maintenance of healthy physiology. Therefore, further work is required to establish the relevance of mitochondria transfer in human health and disease, and if enough healthy mitochondria can practically be administered to humans to influence disease progression.

So it seems to be an area with people interested, but not well understood, especially in humans, and not easily measurable. Hmm