11.1 Challenges Associated with Energy Stress

For cells to function properly, the amount of energy acquired by a cell must be approximately equal to the energy demands of that cell. This homeostatic state is referred to as energy balance, and is maintained through a variety of cellular processes (Figure 11.2). As discussed in Chapter 6.2, cells can acquire energy through the uptake of organic molecules (heterotrophs, e.g., animal cells) or by harnessing other energy sources (like light) to synthesize their own organic molecules (autotrophs, e.g., plant cells). Energy transformed from the oxidation of these molecules powers synthesis of ATP. This ATP can then be used to support processes that require an energy source, such as anabolic reactions, growth, and reproduction. Cells also lose energy to the environment, e.g., in the form of heat. Cells have various mechanisms to maintain energy balance (Figure 11.2), but when these mechanisms fail the cell can experience energy stress.

Factors that Influence Energy Balance

Several factors influence the amount of energy available to a cell, as well as a cell’s energy demand – the amount of energy a cell needs to use. The source of organic molecules (for heterotrophs) or light energy to make organic molecules (for most autotrophs) is important for determining energy available to a cell. For example, a plant cannot grow well in darkness because its energy source (sunlight) is limited. However, even if a cell has access to appropriate organic molecules (e.g., sugar), that energy only becomes available to the cell via metabolic pathways like cellular respiration that can be used to synthesize ATP. This ability to metabolize organic molecules and produce ATP is regulated by abundance and activity of various enzymes. Oxygen availability is also usually important for these reactions because it acts as the final electron acceptor during aerobic cellular respiration, the process that is responsible for the bulk of ATP production in eukaryotic cells. The energy demands of a cell depend on its need to conduct processes that require energy. For example, cells that have high activity levels (e.g., highly motile cells) have high energy demands that must be met to maintain energy balance. This cellular activity also depends on functional proteins, including enzymes.

Energy Stress

Energy stress occurs when a cell is unable to maintain energy balance for prolonged periods, and can occur in two forms: energy limitation or energy excess. Energy limitation can occur when metabolic demand surpasses energy availability, or there is a lack of organic molecules being brought into the cell. One simple example of a condition that induces energy limitation is lack of food availability (starvation). A more complex example of a condition that induces energy limitation is intensive exercise in humans (e.g., running a marathon) where use of ATP due to prolonged physical activity can surpass available ATP production. Cells under hypoxia (oxygen limitation) may experience energy limitation because they cannot produce as much ATP as normal when there is less oxygen available for cellular respiration (Chapter 9) must use anaerobic respiration to produce ATP, which does not produce as much ATP as aerobic cellular respiration. Energy limitation can also arise when temperatures surrounding the cell are reduced. Cold temperatures reduce the function of key enzymes used to process organic macromolecules used in ATP synthesis. This slows down the process of metabolism, placing the cell in an energy limited state.

Cells can be in an energy excess state when organic molecules are overconsumed. When a cell is overconsuming organic molecules or is producing ATP at a rate above consumption it can become energy stressed. One simple example of a condition that induces energy excess is lack of cellular (or organismal) inactivity. During times of cellular inactivity, metabolic demand is reduced, so if the cell continues to metabolize organic molecules as normal there will be more ATP than the cell needs to use. Cells often compensate for low energy demand by storing organic molecules. For example, excess glucose can be stored as glycogen (e.g., in animals) or starch (e.g., in plants). Lipids (fats) are also an effective way to store organic molecules. High reactive oxygen species (ROS) concentrations can accumulate under states of energy excess as well, which can cause oxidative damage (see Chapter 10, and further explanations below).

Cellular Changes Under Energy Stress

Two major indicators of energy balance (or imbalance) are the abundance of ATP and the redox state within a cell. High cellular levels of ATP indicate a high amount of available energy, because this ATP was synthesized via oxidation of organic molecules (nutrients). To help meet the cell’s energy demands, ATP (adenosine triphosphate) is hydrolyzed to ADP (adenosine diphosphate; Chapter 6.3) or AMP (adenosine monophosphate), releasing energy that can be used to power other processes. Thus, the cell is in a high energy state when ATP concentrations are high relative to ADP and AMP. This can happen under energy excess situations, where cells are producing lots of ATP via catabolic pathways like cellular respiration (glucose oxidation). Conversely, the cell is in a low energy state when ADP and AMP concentrations are high relative to ATP. This can happen under energy limitation situations, where cells are consuming lots of ATP through anabolic pathways and other processes.

A second indicator of energy balance is the cellular redox state, which is largely determined by the abundance of reactive oxygen species (ROS). In a normally functioning cell, small amounts of ROS are produced in the same catabolic processes that generate ATP. These ROS are then neutralized by the cell’s antioxidant system, maintaining balance within the cell (Chapter 10). The production of ROS under normal cell functioning indicates that important catabolic processes are taking place as expected in the presence of oxygen. Since ROS are formed during catabolic reactions (such as ATP synthesis) we expect to see more ROS and ATP when energy sources are plentiful relative to a cell’s energy needs. When energy sources are limited relative to a cell’s energy needs, cellular levels of ATP and ROS will be low (Figure 11.3). Ultimately, insufficient ATP under energy limitation can impeded cellular function in many ways, while high ROS production under energy excess can cause cellular damage due to oxidative stress.