September 9, 2020 | David F. Coppedge

Cells Model Sustainable Lifestyles

They renew. They recycle. They clean up their messes. We could learn things from cells.

Cell division: cleaning the nucleus without detergents (Austrian Institute of Molecular Biotechnology). Mitosis, or cell division, is a messy process. All of a sudden, when the nuclear membrane disassembles, genes that had been isolated from the cytoplasm mix with it. Without safeguards, immature messenger RNAs (mRNA) might be prematurely translated by ribosomes. The cell knows how to retrieve each piece that belongs inside the nucleus, and keep out the cytoplasmic organelles, when the nuclear membrane reassembles. A protein called Ki-67 keeps a clean nucleus by undertaking complex and opposite processes:

The research team from IMBA and EMBL have now shown that large components such as ribosomes are in fact removed from the forming nucleus before the nuclear envelope is assembled again. This exclusion process requires the protein Ki-67, which was the focus of an earlier publication in Nature by Sara Cuylen-Häring, the other joint first author of this study, when she was a postdoc in the Gerlich lab in 2016. Dr Cuylen-Häring explains: “We previously showed that Ki-67 was responsible for keeping chromosomes separate in early stages of mitosis by acting as a surfactant. Remarkably, we have now found that it changes its properties at the end of mitosis and performs the opposite function, namely clustering of chromosomes. By coming together into a dense cluster at the end of cell division, chromosomes are able to exclude large cytoplasmic components before the nuclear envelope reforms.”

The Ki-67 protein is important in cancer treatment. Its presence, detected with stains, tells the pathologist how many cells are dividing, and by implication, how aggressive a tumor is.

Autophagy: the beginning of the end (University of Vienna). Another remarkable recycling process is called autophagy (au-TOFF-a-gee). It means “self-eating” (this is one process humans might not want to emulate). A cell might trigger the autophagy process if invaded by bacteria or if its components fail. Cells come equipped with “garbage bags” they make out of protein to surround the damaged or dying parts. Researchers in Vienna found something new about this well-studied process:

Cargoes such as misfolded proteins or damaged organelles are captured in a double membrane-bound compartment called the autophagosome and targeted for degradation. A fundamental question concerns precisely how these “garbage bags” form in the cell. Scientists led by Sascha Martens from the Max Perutz Labs, a joint venture of the University of Vienna and the Medical University of Vienna, have now reconstructed the first steps in the formation of autophagosomes. They show that tiny vesicles loaded with the protein Atg9 act as the seed from which the autophagosome emerges.

Readers can watch a two-minute video clip in the article, and should observe how many pieces are involved in this teamwork effort. It required teamwork, too, for leader Sascha Martens to figure out how the process works:

To understand a complex machinery like the cell, it often helps to take it apart and rebuild it. The biogenesis of autophagosome involves numerous proteins. By isolating and characterizing 21 of these components, the scientists have been able to rebuild parts of the autophagy machinery in the ‘test tube’ – an arduous process that took Sascha Martens and his team almost ten years. “With this approach we could reconstitute the early steps of autophagosome biogenesis in a controlled manner”, he says. With the elaborate toolkit the Martens lab has developed, the scientists now aim to unravel the next steps in the biogenesis of the autophagosome.

That says something about the complexity of this process. After a decade of work, they are still just a little past square one.

Long-term autophagy is sustained by activation of CCTβ3 on lipid droplets (Nature Communications). This open-access paper adds to discoveries about autophagy. A research team in Tokyo wondered where the lipids come from that construct the autophagosome, and how they are recruited. The cell can’t just keep borrowing lipids from the cell membrane, especially when autophagy continues for a long time, or when the cell is starved for nutrients. The scientists identified an enzyme that stimulates formation of propargylcholine (PC), which recycles lipids from waste products.

The paper gets bogged down in abstruse details, but tells something interesting in the Introduction about garbage removal. Cell garbage is put into autophagosomes, but the actual recycling occurs in lysosomes (‘ripping bodies’). How do the two meet up?

Upon induction of autophagy, membrane sacs called isolation membranes form and elongate to enclose various contents, and become double-membrane structures called autophagosomes. Autophagosomes fuse with lysosomes for degradation of the engulfed material.

The paper shows how cells can handle wealth and poverty. When nutrients are plenty, autophagy works. When cells are starved of nutrients, autophagy works with alternate methods.

Someone had the foresight to handle all these complex details. Otherwise, cells and animal or plant bodies might just melt into piles of biological garbage. This is one reason to thank God before eating. That food is going inside of you to support incredibly complex processes that scientists continue to unravel bit by bit. Aren’t you also thankful that eating is usually pleasurable?

Incidentally, none of these articles and papers mentioned evolution. The Darwin Party may claim that “nothing in biology makes sense except in the light of evolution,” but don’t believe it. Real empirical science work at the level of cells rarely mentions evolution. Sometimes there are passing references to it, using the “it evolved” meme, or when a confession is made that some process or gene is “evolutionarily conserved” (unevolved). The only time Darwin comes up is when politics is involved, or when the Darwin Party wants to push its materialistic philosophy. Otherwise, Charlie’s quaint Victorian myth is pretty useless.

 

 

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