MCAT Content / Oxidative Phosphorylation / Mitochondria Apoptosis Oxidative Stress

Mitochondria, apoptosis, oxidative stress

Topic: Oxidative Phosphorylation

Oxidative phosphorylation can result in the production of deleterious reactive oxygen species (ROS) in the mitochondria when oxygen molecules are improperly reduced; however, this excessive oxidative stress can be remedied by apoptosis, or programmed cell death.

The mitochondria is the site of metabolic pathways like the Krebs cycle and the electron transport chain that allow our cells to produce ATP. However, it also plays a role in apoptosis, a form of programmed cell death. Note the distinction between necrosis, an uncontrolled form of cell death that usually occurs in response to extreme stress, and apoptosis, which is controlled and often confers an advantage to an organism. For example, during embryonic development, the digits on our hands are “carved” out of an initial paw-like structure through apoptosis of the unwanted tissue, ultimately producing a hand with five separate fingers.

In addition to sculpting tissues during embryonic development, apoptosis can be triggered by various other factors. These include extensive DNA damage that cannot be repaired by DNA repair mechanisms, viral infection, environmental stress (such as oxygen or nutrient deprivation), and a loss of physical proximity or a chemical signal (such as growth factors) from neighboring cells.

Apoptosis can also be triggered by reactive oxygen species (ROS), which are oxygen molecules with an unstable number of electrons that are highly reactive and can result in toxic reactions with cellular components like DNA, proteins, and lipid membranes. ROS include the negatively charged superoxide anion, the neutrally charged hydroxide molecule, and hydrogen peroxide, which can be formed in our cells. Recall that oxygen is the final electron acceptor in the electron transfer chain, necessary for the production of ATP. However, up to 4% of oxygen molecules are improperly reduced during oxidative phosphorylation, leading to the production of ROS. Although enzymatic mechanisms exist to convert ROS to less reactive species, extensive oxidative damage can induce apoptosis.

Mitochondria play a significant role in initiating apoptosis, and one of the first steps is increased permeability of the outer mitochondrial membrane. This process is regulated by proteins in the BCL-2 family. Note that BCL-2 family proteins include both pro-apoptotic proteins, those that drive apoptosis forward, and anti-apoptotic proteins, those that normally prevent it. When the mitochondrial membrane becomes more permeable, cytochrome C, the shuttle between complexes III and IV of the electron transport chain, is released from the inter membrane space into the cytoplasm. Once in the cytoplasm, cytochrome C activates a family of enzymes called caspases, which act as proteases to initiate large-scale protein degradation, and nucleases, to degrade DNA. Together, these processes result in regulated cellular breakdown; these components may then be phagocytosed by neighboring cells for reuse.


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Key Points

• Reactive oxygen species (ROS) are produced during oxidative phosphorylation at the electron transport chain in the inner mitochondrial membrane.

• Excessive accumulation of ROS can lead to damaging oxidative stress.

• Oxidative stress can initiate apoptosis, or programmed cell death, to protect neighboring cells from damage.

• Apoptosis can be initiated at the outer mitochondrial membrane by BCL-2 family proteins, leading to increased membrane permeability, release of cytochrome C into the cytoplasm, and activation of cytoplasmic caspases and nucleases.

Key Terms

Reactive oxygen species (ROS): Highly reactive oxygen molecules with unstable electrons; includes the superoxide anion, hydroxide, and hydrogen peroxide.

Apoptosis: Controlled or programmed cell death, which is used to confer an advantage to an organisms, such as regulation of development or protection from ROS.

Oxidative stress: The deleterious, excessive accumulation of ROS in a cell.

Caspases: Enzymes that act as proteases to break down proteins during apoptosis.

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