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Are Exophers Present in Various Cell Types?

Image credit: Zhang et al. 2016 (https://www.cell.com/cell-systems/fulltext/S2405-4712(16)30293-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2405471216302939%3Fshowall%3Dtrue#supplementaryMaterial)

Jamila Aug 07, 2020
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Does the exopher system exist in different cell types? or is it a neuronal-specific junk removal system?

Researchers have observed that mouse hippocampal neuronal cells (HT22 cells) and the neurons of C. elegans expel a large vesicle called an exopher. These exophers can remove toxic protein aggregates (such as amyloid-beta, tau, and a-synuclein), lysosomes, and even mitochondria.

In a recent study by Turek and colleagues, it was found that the body wall muscles cells of c. elegans could produce exophers. The exophers produced by the muscle cells contained proteasomes and a small number of mitochondria. Furthermore, the researchers report that exophers derived from the muscle cells were produced in the same way as neuronal exophers. This study suggests that exophers may not be a waste removal system only for neuronal junk, exopher systems may be present in the various tissue and cell types.

Further research needs to be conducted in non-neuronal cells to show the presence of further exopher systems and if they do exist, what do these exophers precisely carry in their cargo?

[1]Fu, Hualin, et al. "Metabolic wastes are removed by excretosomes, nanotubes and exophers in mouse HT22 cells through an autophagic vesicle clustering mechanism." bioRxiv (2019): 699405.

[2]Melentijevic, Ilija, et al. "C. elegans neurons jettison protein aggregates and mitochondria under neurotoxic stress." Nature 542.7641 (2017): 367-371.

[3]Turek, Michal, et al. "Nutritional status and fecundity are synchronised by muscular exopheresis." bioRxiv (2020).

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Jamila Nov 26, 2020
Recently, researchers reported that cardiomyocytes release exophers too!

Bartelt and Weber found that cardiomyocytes released exophers containing cellular junk (dysfunctional mitochondria) to resident cardiac macrophages - the resident cardiac macrophages digested the exophers. However, when the resident cardiac macrophages were absent, this caused cardiac stress leading to less ATP production, mitochondrial dysfunction, inhibition of autophagy, and exophers piled up in the extracellular space of the myocardium.

Although the researchers still aren't sure what role exophers have in health and disease. This research proves that exopher systems are present in non-neuronal cell types too.

It would be interesting to see whether more non-neuronal cell types have this system in place. It could be a waste removal system for all cell types!?

[1]Bartelt, Alexander, and Christian Weber. "Mitochondrial Ejection for Cardiac Protection: The Macrophage Connection." Cell Metabolism 32.4 (2020): 512-513.

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