Biological complexity: repairing lysosomes (Introduction)

by David Turell , Monday, March 20, 2023, 14:12 (403 days ago) @ David Turell

Essentially garbage collectors cleaning up cells:

https://www.the-scientist.com/news-opinion/scientists-uncover-major-pathway-cells-use-t...

"Lysosomes are tiny sacs of digestive enzymes that declutter cells by breaking down waste. But they can also be troublesome: When their outer surface is damaged, their destructive proteins begin to spill into the cytoplasm and harm the cell. Indeed, the frequency of this leakiness increases as a person ages and likely plays a role in aging-associated diseases such as neurodegenerative conditions.

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"Further experiments revealed that when the lysosome membrane is compromised, an enzyme called phosphatidylinositol-4-kinase type 2a, or PI4K2A, is recruited to the organelle’s surface, possibly in response to calcium ions leaking out of the lysosome, says Toren Finkel, a study coauthor and a professor of medicine at the University of Pittsburgh. PI4K2A generates a lipid called phosphatidylinositol-4-phosphate (PI4P), which acts as a danger signal and recruits several proteins known as ORPs (for oxysterol-binding protein-related proteins), which tether the endoplasmic reticulum to the lysosome.

"These ORPs then swap PI4P with lipids from the endoplasmic reticulum, including phosphatidylserine, which recruits the lipid transporter ATG2—the final component of the pathway. “ATG2 is like a firehose” for lipids, says Finkel, pumping molecules into the membrane to plug the hole.

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"As an ode to the University of Pittsburgh, the two scientists christened the pathway phosphoinositide-initiated membrane tethering and lipid transport, or PITT for short.

"Tan believes that the two mechanisms have evolved to repair different types of damage, with the ESCRT complex mending small pores while the PITT pathway repairs larger holes.

"The new pathway may be performing most of the cell’s handywork. The researchers found that cells usually take around an hour to repair damaged lysosomes, but this healing requires up to 11 hours in cells lacking PI42KA. “It looks like quite a significant pathway, perhaps more so than the ESCRT pathway,” says Antony Galione, a pharmacologist at the University of Oxford in the UK who was not involved in the study."

Comment: It is my view the first bacteria appeared all at once, fully designed. In that view, lysosomes were present from the beginning, fully functional. I f not the first cells would have died of their own byproducts. Irreducible complexity, as implied, the cell was designed with all its parts fully functioning.