Biological complexity: mitochondrial repair (Introduction)

by David Turell , Friday, July 28, 2023, 17:41 (274 days ago) @ David Turell

For any sort of damage or stress:

https://phys.org/news/2023-07-mitochondria-stress.html

"...This is referred to as the endosymbiotic theory, according to which that one single-celled organism was the primordial mother of all higher cells, out of which all animals, fungi and plants developed. Over the course of billions of years, the encapsulated bacterium became the cell's powerhouse, the mitochondrion, which supplies it with the cellular energy currency ATP.

"It lost a large part of its genetic material—its DNA—and exchanged smaller DNA segments with the mother cell. However, now as in the past, mitochondria divide independently of the cell and possess some genes of their own.

***

"A certain type of mitochondrial stress is caused by misfolded proteins that are not quickly degraded and accumulate in the mitochondrion. The consequences for both the mitochondrion and the cell are dramatic: Misfolded proteins can, for example, disrupt energy production or lead to the formation of larger amounts of reactive oxygen compounds, which attack the mitochondrial DNA and generate further misfolded proteins. In addition, misfolded proteins can destabilize the mitochondrial membranes, releasing signal substances from the mitochondrion that activate apoptosis, the cell's self-destruction program.

"The mitochondrion responds to the stress by producing more chaperones (folding assistants) to fold the proteins in order to reduce the misfolding, as well as protein shredding units that degrade the misfolded proteins. Until now, how cells trigger this protective mechanism was unknown.

***

"The result is that the mitochondria send two chemical signals to the cell when protein misfolding stress occurs: They release reactive oxygen compounds and block the import of protein precursors, which are produced in the cell and are only folded into their functional shape inside the mitochondrion, causing these precursors to accumulate in the cell. Among other things, the reactive oxygen compounds lead to chemical changes in a protein called DNAJA1. Normally, DNAJA1 supports a specific chaperone (folding assistant) in the cell, which molds the cell's newly formed proteins into the correct shape.

"As a consequence of the chemical change, DNAJA1 now increasingly forces itself on the folding assistant HSP70 as its helper. HSP70 then takes special care of the misfolded protein precursors that accumulate around the mitochondrion because of the blocked protein import. By doing so, HSP70 reduces its interaction with its regular partner HSF1. HSF1 is now released and can migrate into the cell nucleus, where it can trigger the anti-stress mechanism for the mitochondrion.

"As Münch explains, "It was very exciting to discover how the two mitochondrial stress signals are combined into one signal in the cell, which then triggers the cell's response to mitochondrial stress. Moreover, in this complex process, which is essentially driven by tiny local changes in concentration, the stress signaling pathways of the cell and the mitochondrion dovetail very elegantly with each other—like the cogs in a clockwork.'"

Comment: this is more easily explained by God, the designer, solving problems than chance mutations doing it.