13.5 Hypoxia Stress [in progress]

Recall from Chapter 9 that hypoxia (hypo= below, under; oxia= oxygen levels) is when there is not a sufficient oxygen supply available to meet the cell’s energy requirements. Hypoxia can result due to low oxygen supply, such as when an organism is in an oxygen-limited environment. Freezing is hypothesized to cause hypoxia, and this chapter section will explore how this happens and how cells can tolerate this stressor during freezing.

When hypoxia occurs

During the process of freezing and thawing, hypoxia stress can occur during the frozen stage (Figure 13.2). In animals with a closed circulatory system, hypoxia can also occur if the circulatory fluid freezes, because the delivery of oxygen to cells cannot occur via a frozen circulatory system. In animals with an open circulatory system, hypoxia may occur because ice has limited permeability to oxygen. Therefore, if the liquid surrounding the cell freezes, the cell becomes encased in ice, and oxygen can no longer enter the cell. The lack of oxygen available to the cell causes hypoxia stress. 

[figure showing ice-encased cell? Or perhaps circulatory system]

Impact of hypoxia on cells and their macromolecules

Hypoxia stress does not directly impact DNA, lipids, or proteins in the cell. However, it does impact the concentration of ATP available for cellular processes. When hypoxia occurs, low oxygen availability prevents the mitochondrial electron transport system (ETS) from functioning, which then prevents ATP from being created via oxidative phosphorylation. Without a functioning ETS the concentration of ATP produced by the cell decreases. If the concentration of ATP becomes too low, the cell is unable to perform normal cellular processes such as transmembrane ion transport, anabolic pathways (protein synthesis, lipid synthesis, DNA and RNA synthesis), and other forms of cellular work.

Without sufficient oxygen supply, cells need to use fermentation, a process that regenerates NAD⁺ in order to continue using glycolysis to produce ATP (see Chapter 9.3). However, fermentation is not the most ideal reaction for cells to generate ATP because it produces lactate or other molecules that are slightly toxic to cells. In addition, the amount of ATP being produced from fermentation is much less than that of oxidative phosphorylation. The accumulation of lactate in the frozen state can ultimately cause damage to the cell because lactate is an acid that alters cellular pH.

Mechanisms that protect cells from hypoxia stress

The major mechanism cells can employ to mitigate hypoxia stress during freezing is to modify (and generally decrease) their metabolic activity. Metabolism can be altered in different ways, such as by increasing stored energy reserves before freezing, or by decreasing metabolism. As described above, increasing the rate of anaerobic respiration via fermentation is a core mechanism to continue generating ATP via glycolysis in the absence of oxygen. Many organisms increase nutrient acquisition prior to freezing in order to increase their energy reserves, which often take the form of glycogen. Increasing stored energy reserves ensures there will be a sufficient amount of glycogen available to enter glycolysis and produce ATP via anaerobic respiration for long periods. In contrast, suppressing the metabolism of an organism while it is frozen assists in reducing the amount of energy required for survival.

[figure summarizing these metabolic adjustements?]