Biochemical controls: alternate cellular waste disposal (Introduction)

by David Turell , Wednesday, June 12, 2024, 17:41 (162 days ago) @ David Turell

A look at myocardial cells:

https://www.the-scientist.com/taking-out-the-trash-an-alternative-cellular-disposal-pat...

"Gustafsson’s laboratory determined that cardiac myocytes and other cells use secretion to remove mitochondria from the cell when lysosomal degradation is inhibited.

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"Mitochondria generate most of the cell’s energy. However, when they become dysfunctional, damaged, or old, mitochondria can turn into pro-death organelles, which produce reactive oxygen species that damage the cell’s proteins and DNA. This is a major problem for cardiac myocytes, which rely on the energy produced by mitochondria to contract. Additionally, the body cannot replace these particular cells because they do not divide.

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"We discovered that fibroblasts and cardiac myocytes secrete mitochondria inside extracellular vesicles (EV) when their lysosomal function is compromised or overwhelmed. This encapsulation ensures that the mitochondria do not elicit a dangerous immune response once outside the cell because of their bacterial origin. The mitochondria-containing EV originate from within multivesicular bodies (MVB), which either deliver the cargo to the lysosomes for degradation or ship everything to the plasma membrane for secretion. We found that Rab7, a protein present on the MVB’s outer membrane, is a regulator involved in dictating the fate of the vesicles. We believe that active Rab7 directs the EV toward the lysosomes, but in the absence of this protein or when it is inactive, the cell will traffic the EV to the plasma membrane. (my bold)

"Once cardiac myocytes release the mitochondria-containing EV, resident cardiac macrophages and other cells in the heart internalize the vesicles to degrade them through their lysosomes. The EV do not seem to enter circulation but stay within the heart. Ultimately, this is an alternative garbage disposal pathway used by cells to get rid of dysfunctional and damaged mitochondria when they cannot degrade the organelles in their own lysosomes."

Comment: as usual, I have pointed out a control mechanism that requires a specific protein as the control mechanism (Rab7). It is very unlikely that chance evolution can be so specific. Only design fits.