The process of energy production begins in the cytoplasm through a biochemical process known as glycolysis (14) (Figure 4). Glycolysis generates four molecules of ATP for every two molecules of glucose that are invested in this process of enzymatic reduction. A bi-product of glycolysis is lactate that can be used as a substrate for other biochemical reactions. The ATP generated by glycolysis is the primary source of ATP for fast replicating cells such as stem cells to mediate, for example, cell division and DNA replication (15). It is also be used by tissues and fibres that require an immediate supply of energy. For example, immune cells that are associated with a rapid response to an infection and are rapidly recruited from a stem cell pool predominantly use glycolysis to generate energy to mediate their response (16). Sperm cells are another example of cells that primarily rely on glycolysis (17). Indeed, sperm cells have between 22 and 70 mitochondria that are localised to the midpiece of this cell (18) and their mitochondrial location and number compare very differently with oocytes (Figure 5). Similarly, the muscle fibres of athletes, such as sprinters and jumpers, who require a fast-twitch reaction to perform an explosive series of movements over a short period of time, primarily utilise glycolysis (19).

The substrates generated from glycolysis, in particular pyruvate, can feed into the citric acid cycle where they generate electron donors that enter the electron transfer chain (20) (Figure 4). Furthermore, each of these pathways, along with glycolysis, individually contributes electron donors to the electron transfer chain. The electron transfer chain is where aerobic respiration takes place, namely oxygen is metabolised in order to generate ATP through the biochemical process of OXPHOS (14). Specifically, electrons enter the chain and pass through each of the initial four complexes. As a consequence, protons (H+ ions) are pumped through three of these complexes to establish the mitochondrial membrane potential. Protons then return into the mitochondria via the ATPase (complex V) resulting in the generation of ATP from ADP. Unlike glycolysis, OXPHOS generates between 68 and 76 molecules of ATP from the two molecules of glucose that are initially invested at the start of glycolysis (14). Consequently, the electron transfer chain plays a major role in ensuring that sufficient energy is available for cells and tissues that have a high requirement for energy. Typically, neurons and cardiomyocytes require energy from this source to mediate intracellular events such as action potentials and to maintain pacemaker-like function (discussed in (21)).

Decreased levels of energy production from OXPHOS can lead to severe metabolic type diseases (22). Likewise, failure to establish the mitochondrial membrane potential can result in disruption to cellular function, loss of ATP generation, increases in free radical activity, which, in turn, can initiate programs of cell death (23, 24). Indeed, some of the mitochondrial pathways are clearly evidently associated with the regulation of cell death where, for example, disruption to mitochondria can lead to the release of cytochrome C that activates the caspase pathway, which targets the nucleus for disruption and ultimately results in the death of the cell (25).