The importance of taking out the trash: An overview of cellular protein degradation pathways

This might not be obvious, but cells generate a lot of garbage.

Like anything, parts of cells get damaged or worn out and eventually need to be replaced.

This is true of small proteins all of the way up to mitochondria or other large organelles.

Some cells, like those in our immune system, even EAT THINGS like bacteria or viruses which are really just juicy bags of protein that need to be degraded!

But it’s not only broken proteins or microbes that get disposed of.

During development, cell division, or even throughout the day, a cell’s needs change.

This means that the proteins that are present also need to change!

This is especially true when cells ‘differentiate’ into all of the different cells that make up our organs and tissues.

And, if you remember, YOU are the product of one sperm and one egg that divided into trillions of different cells!

To get from a fertilized egg to YOU, changes in protein content within all of those cells needed to be made.

And the changing protein needs of cells are, in part, regulated by protein degradation pathways!

There are two major ways to chop up proteins in a cell:

The Proteasome - These are like protein wood chippers. They’re used to help with the rapid proteolysis (big word for chopping) of useless, misfolded, damaged, or no longer needed proteins!

The proteasome is itself a protein complex that recognizes a specific tag on proteins marked for destruction and dices them up into ~7 amino acid chunks.

Those chunks can then be further degraded and reused to create new proteins!

The tag that the proteasome recognizes is a 76-amino acid protein called ubiquitin.

And this tag is added by a grim reaper-like protein called ubiquitin ligase.

Once a chain of at least 4 ubiquitins is added to a protein, it is recognized by the proteasome and gobbled up.

The Lysosome - If the proteasome is a wood chipper, then the lysosome is like an industrialized garbage dump.

The lysosome is a specialized membrane enclosed organelle (kind of like a bathroom inside a house) where bulk protein degradation activities take place.

They’re filled with proteases (small protein chomping enzymes) and have a highly acidic environment to aid in the breakdown of whatever is unfortunate enough to end up in there.

The lysosome is used for digesting nutrients that have been brought in from outside the cell, degrading proteins that have hung around for too long, disassembling and recycling major cellular organelles like mitochondria (autophagy), or bulk destroying proteins during times of stress.

And it's probably not surprising that problems with both the proteasome and the lysosome are implicated in many diseases.

Because, proteostasis, or the maintenance of the proteome through the creation and destruction of proteins, is key for normal cellular function!