14.3 Degradation and Replacement of Damaged Macromolecules [in progress] (74/44) -- Online Textbook for Biol 395

14.3 Degradation and Replacement of Damaged Macromolecules [in progress] Key Concepts By the end of this section, you will be able to do the following: - Describe which types of stress can cause sufficient damage to macromolecules and organelles that they need to be degraded - Describe mechanisms to degrade damaged proteins and organelles - List processes that can be used to replace damaged proteins and organelles Under extreme stress, macromolecules such as proteins, lipids, and DNA can be permanently damaged. Organelles may also be damaged, depending on the nature of the stress. If macromolecules and/or organelles are damaged beyond repair, the stress response will often involve degrading these damaged components and replace them, although not everything that is damaged can be replaced. For example, it is difficult to replace DNA and membranes (composed of lipids) that have experienced irreparable damage; damage to these cellular components usually lead to cell death (Chapter 14.5) if the damage cannot be repaired (Chapter 14.2). In this chapter, we focus on the degradation of proteins and organelles, which can often be replaced as long as the cell has sufficient resources to do so. The two types of degradation are proteasomal degradation (degrades proteins) and autophagy (degrades many types of macromolecules and organelles). The products of degradation can then be used to synthesize replacements. Proteasomal degradation [potential to expand the details] Most kinds of stress can cause proteins can become denatured and aggregated. For example, extreme heat, extreme cold, osmotic stress, and oxidative stress can all cause irreparable protein damage. These damaged and aggregated proteins are non-functional and potentially toxic to the cell. Instead of inducing cell death, the cell can degrade specific proteins and synthesize new ones. Proteins to be degraded are tagged with ubiquitin and then degraded by proteasomes (Figure 14.10). Proteasomes are large protease and ATPase complexes that degrade tagged proteins into small peptides using ATP (Figure 14.10). The peptides can then be further broken down into amino acids by other processes, and those amino acids can then be used in the synthesis of new proteins for the cell. Figure 14.10 Ubiquitin tags irreparable proteins to be degraded in amino acids through proteasomal degradations. (Image: https://www.nejm.org/doi/10.1056/NEJM199612193352507) [copyright – likely have to replace] Autophagy Autophagy (self-eating) is a natural, self-degrative process that cells perform to remove damaged cell organelles like mitochondria and peroxisomes as well as old/damaged proteins. This process relieves the cell from various stress conditions such as starvation and cell damage. Autophagy can be selective or non-selective when removing damaged organelles and protein aggregates. There are two types of autophagy conserved in eukaryotes: microautophagy and macroautophagy (Figure 14.11). Even though they have distinc