Autophagy

First, a few definitions.

Amino Acid: Amino acids are organic compounds that contain amine (a derivative of Ammonia) and carboxyl functional groups (a double-bonded carbon atom linked to an oxygen group and a hydroxyl group through a single bond), along with a side chain specific to each amino acid. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen, although other elements are found in the side chains of certain amino acids.

Protein: Hey, we read about them every day so we all know what they are…. Now look it up in Wiki.. any the wiser?  Just think of them as an awful lot of Amino Acids (and a few other things) joined together in many different forms.

RNA/DNA: Ribonucleic acid is a polymeric molecule essential in various biological roles in coding, decoding, regulation, and expression of genes. RNA/DNA are nucleic acids, and, along with lipids, proteins, and carbohydrates, constitute the four major macro-molecules essential for all known forms of life. (mRNA ring any bells? It transfers information from the genome into proteins by translation)

Gene:  That double Helix thingy. What your teacher at school probably called “the blueprint for life.”  Better in this case perhaps to think of it as “the blueprint for Proteins.”

So the Genetic Code says, take these specific Amino Acids (and a few of these other things) stick them together to form a Protein, fold that Protein up to give a Functional Protein, which might drive metabolism, or growth, or become the structural foundation for a Cell, oh and while you are about it, adjust the internal cell environment.

Cell: “The smallest structural unit of an organism that is capable of independent functioning, consisting of cytoplasm, usually one nucleus, and various other organelles, all surrounded by a semipermeable cell membrane.”

Well that is as clear as mud. Think of a leaky balloon, filled with mucky liquid with an egg floating in it.  (The muck in the liquid is important.) People are often unaware that their body contains not one cell that they were born with, cells are constantly being renewed, some quite quickly.

This has been well studied but, what happens when Proteins get old or lose their function?

PROFESSOR OHSUMI LOOKS AT YEAST

(and wins a Nobel Prize for doing it)

Yoshinori Ohsumi had a big idea, now many people go through life without ever having a big idea, but he most certainly did, and it is people with big ideas that change the world.

He wanted to know how the mechanism within a Cell managed to break down certain components of the cell so that the Cell could recycle them.  As Prof. Ohsumi noted, “Life is a balance of protein synthesis and protein degradation,”

Earlier a group of scientists had discovered a Cellular function which appeared to be driven by a common protein called Ubiquitin, (cool name eh?) they called it ubiquitin-mediated Protein degradation, in which parts of the Cell seemed to degrade proteins one by one. However, this didn’t explain how the Cell got rid of old worn out parts of itself.

AUTOPHAGY (Self-eating)

An intercellular degradation mechanism, best described as the Cell recycling the older bits inside it. It has been known about for 60 years but nowhere near fully understood.

This is where Professor Ohsumi had his big idea. Since human cells (all 600 trillion or so of them in each of us) are somewhat different and complex, he decided to study much simpler Yeast cells. Bit of an understatement there, Yeast is a single cell organism.

What he was trying to observe under a normal microscope was whether Autophagy was taking place, and he surmised that if he could starve the Cell then things called Autophagosomes would accumulate within the Cell and become visible. There are several ways to starve a cell; look them up if you are interested.

Don’t you just love how Scientists come up with big words to describe something quite “simple,” it’s almost as if they don’t want us ordinary folk to understand what is going on. An Autophagosome is eventually, a spherical structure within the Cell and it has a double membrane surrounding it, but it doesn’t start like that. Think Pakman!   A C shaped portion of the Cytoplasm (the mucky liquid, I said it was important) wraps itself around those old or damaged Proteins, or even around invading bacteria and viruses, eventually surrounding them completely, becoming an Autophagosome. This then fuses with a Lysosome in the cell.

Lysosomes are sphere-shaped sacs filled with hydrolytic enzymes that have the capability to break down many types of biomolecules.

The Lysosome then “operates” on it, and its contents keeping the bits it needs to help the Cell survival, whilst dumping the rest. In the process it rips apart anything damaged including any bacteria or virus.

The best way to think of a Lysosome is that it is like your local Tip. You drive in (Auto-phagosome) and offload your garbage to specific containers. Some of the stuff you dump will be recycled, some will be buried in a landfill etc. Or, in the case of my local authority chuck the lot into landfill.

Ohsumi did a bit of magic, he starved a Yeast Cell, which kicked off production of Autophagosomes within it, as the Cell started eating itself to survive. All of which he could see happening!

Now Autophagy has 3 broad roles in the Cell:

Firstly, it is a turnover mechanism, Cells break down parts of their old components and convert them to new components.

Secondly, it is a response to nutrient starvation. Starve the Cell, and it breaks down some components and synthesises the bits it needs to survive.

Thirdly, the elimination of Pathogens, in that the Cell breaks down Pathogens to prevent infection.

By proving these mechanisms existed Ohsumi had a method to identify and characterise the Genes involved in this process. Within a year he had identified the first Gene (ATG1) necessary to make Autophagy work. Thereafter he studied and identified the proteins and protein complexes that controlled the formation of the Autophagosome. Now that got him a well deserved Nobel Prize, and also opened up a whole new area of research into the effects on illness and disease.

Cancer cells use about 10 times the sugar that a normal cell does, and there are now methods available to starve them whilst minimising the effect on healthy cells. Starve a Cancer cell of sugar, and it dies. Technically that is called Apoptosis, and for example, using an antibiotic called Bafilomycin A1 to target the autophagosome and to stop it functioning, kicks the cell into Apoptosis. This has now been induced in cells related to Osteosarcoma (in vitro.) ( https://www.spandidos-publications.com/10.3892/mmr.2014.2281)

For those of you trying out a fasting regime to lose weight, this is where the idea for that came from. You are in effect clearing out the older Cell components and building new ones. (Be aware that if you are on a standard western diet it can take a very long time to get to Ketosis, a 16/8 regime just doesn’t do that. If you are on a real Keto diet and have been for a while then you should already be running on Ketones. Recently intermittent fasting has become interesting for those that believe in a post-vaccine treatment protocol, where intermittent daily fasting stimulates the clearing of cells that are damaged and any damaged mitochondria and foreign proteins. That last bit could be important.  However,  if you want to try a fasting regime it is not to be taken lightly so discuss it with a Doctor first, especially if you have any current medical conditions. https://covid19criticalcare.com/treatment-protocols/ might be worth a read.

Here is a much deeper description of what is going on, or at least what has been determined so far, not so simple.  https://www.nature.com/articles/s41576-022-00562-w
 

© FJ 2024