Functions and Roles of Mitochondria in Cells

Traditionally referred to as the powerhouses of cells, mitochondria play a vital role in the conversion of food into energy for biological processes in cell biology. However, in recent years, a growing number of studies have demonstrated that mitochondria are also deeply involved in a range of other activities that enable cells to function efficiently and help to maintain a healthy body.

Mitochondria definition

Mitochondria (mitochondrion, singular) are membrane-bound organelles found in the cytoplasm of almost all eukaryotic cells but are absent in prokaryotic cells. The main function of mitochondria is to generate the energy needed to power a cell’s biochemical reactions in the form of adenosine triphosphate (ATP). Mitochondria have their own set of DNA referred to as mitochondrial DNA (mDNA). Generally, mitochondria and therefore mDNA are inherited maternally.

Mitochondria structure

Mitochondria are small, often between 0.75 and 3 µm in size. An overview of many of the primary components of the mitochondria is depicted in the mitochondria diagram in Figure 1:

Figure 1: The key structures present in mitochondria. Credit: Technology Networks. 

• Outer membrane: The outer membrane is permeable to ions and small proteins due to the abundance of large conductance channels, known as voltage-dependent anion channels (VDAC).
• Inner membrane: The inner membrane is an ion-impermeable membrane that folds to form cristae in the interior of the mitochondrion.
• Intermembrane space: The intermembrane space is the sub-compartment formed between the inner and outer mitochondrial membranes.
• Ribosome: Ribosomes are responsible for protein synthesis.
• Cristea: Cristea are folds in the inner membrane that increase the overall surface area of the membrane, allowing a greater number of enzymes involved in ATP synthesis to be packed into the mitochondria.
• Matrix: The matrix contains the mitochondrial DNA as well as the enzymes responsible for the central reactions involved in oxidative metabolism.
• Mitochondrial DNA: Human mitochondrial DNA consists of 6,569 DNA base pairs and, unlike the chromosomes found in the nucleus, the mitochondrial genome is circular.

Mitochondria function

Below we take a look at five functions and roles that mitochondria have been shown to play in cells, and what can happen when these processes are disturbed.

1. Adenosine triphosphate (ATP) production

Perhaps the most well-known function of mitochondria is the production of ATP, the energy currency of cells.

What is ATP?

ATP is the source of energy for use and storage at the cellular level. It is a nucleoside triphosphate, consisting of adenine, a ribose sugar and three bonded phosphate groups. The breakdown of ATP to adenosine diphosphate (ADP) through hydrolysis of a phosphate group provides readily releasable energy.

How is ATP produced?

The majority of ATP synthesis occurs in cellular respiration within the mitochondrial matrix. In cellular respiration, the enzyme ATP synthase converts ADP and phosphate to ATP. ATP synthase is located in the inner membrane of the mitochondria.

Where is ATP stored?

Once synthesized, ATP is stored inside the mitochondrial matrix or it can be transported into the intermembrane space of the mitochondria by the nucleotide exchanger adenine nucleotide translocase, which passively exchanges ATP with ADP. Once in the intermembrane space, ATP can freely pass through the outer membrane via VDAC.

Health disorders related to mitochondrial ATP production

The complex, multistep process of ATP synthesis, is essential for the proper functioning of the body, and dysfunction can contribute to a variety of diseases ranging from diabetes and Parkinson’s Disease, to rare genetic disorders.

The greatest metabolic demand in the body is found in the outer retina, a site which also has a high concentration of mitochondria. A team of researchers from University College London (UCL) demonstrated that a reduction in retinal ATP was associated with inflammation and the subsequent development of age-related macular degeneration. It is thought that similar declines in ATP production throughout the body could play a role in a number of other aspects of aging.

Researchers from Columbia University found an association between positive psychosocial experiences and a greater abundance of the mitochondrial energy transformation machinery. Although there was a greater abundance of mitochondrial energy transformation-related proteins in the brain cells of participants with higher psychosocial scores, the researchers do not yet know if that leads to greater energy transformation.

Mitochondria structure and function. Credit: sci-ology via YouTube.

2. Calcium homeostasis

Mitochondrial calcium exchange is the flow of calcium in and out of a cell’s mitochondria, a process important in metabolic regulation and cell death. Mitochondria store calcium and work in synergy with organelles such as the endoplasmic reticulum to control the calcium concentration in cells. Mitochondrial calcium levels have been linked to mitochondrial dynamics, function and metabolism.  

Calcium efflux from mitochondria has been identified as playing a vital role in heart function. Knocking out the gene encoding the mitochondrial sodium/calcium exchanger (NCLX) in mice was associated with sudden death from heart failure, whilst overexpression increased mitochondrial efflux and offered protection against heart failure progression. The findings suggest that NCLX maintains cardiomyocytes by regulating calcium efflux and preventing calcium overload-induced cell death.

Mitochondrial malfunction has been proposed as an early event in Alzheimer’s disease and other age-related neurodegenerative disorders. Researchers found that increased mitochondrial calcium levels were associated with plaque deposition and neuronal death in a mouse model of cerebral β-amyloidosis, a condition in which amyloid proteins build up on the walls of the arteries in the brain leading to strokes and dementia.

3. Regulation of innate immunity

Innate immunity is the in-born system that recognizes and responds to infection by pathogens, providing immediate, non-specific defense. Researchers have found that T cells are particularly sensitive to genetic disturbances in mitochondrial DNA. Additionally, patients with Pearson syndrome have deletions in their mitochondrial DNA that result in their T cells not having enough energy to perform their various functions.

The MAVS signaling pathway

Mitochondrial antiviral signaling protein (MAVS) plays a key role in the innate response to viral infections, helping to induce antiviral and anti-inflammatory pathways.

Upon recognition of a virus, MAVS induces activation of the transcription factors interferon regulatory factors 3 and 7 and nuclear transcription factor-κB (NF-κB). This process ultimately leads to the expression of multiple proinflammatory factors and antiviral genes, which inhibit viral replication and transmission.

Disruption to MAVS can lead to a break down in immune protection – an increase in severe mortality and death from experimental colitis was seen in MAVS knockout mice compared to wild type animals.

4. Programmed cell death

Apoptosis is the highly controlled process of programmed cell death used by multicellular organisms in a number of biological processes, including intrauterine development, mopping up damaged cells and maintaining cell numbers. The production of apoptotic bodies, which are engulfed by phagocytes, can be activated by both an intrinsic and extrinsic pathway.

Mitochondria control the intrinsic pathway, releasing proteins including cytochrome c from their intermembrane space in response to cell stresses such as heat, infection, hypoxia, increased calcium and nutrient deprivation. Disturbances to this regulation are associated with the development of diseases such as cancer and tissue damage following stroke.

5. Stem cell regulation

Mitochondria are thought to play crucial roles in the maintenance of pluripotency, differentiation and reprogramming of induced pluripotent stem cells.

The generation of reactive oxygen species (ROS) by mitochondria has been shown to regulate somatic stem cell fate. An increase in ROS is associated with a decrease in the regeneration potential of human mesenchymal stem cells and a move towards progenitor commitment and differentiation.

This handful of examples gives just a snapshot of the mighty influence that mitochondria can have on cell function and health. The continued discovery of these intricacies, and the mechanisms involved in mitochondrial dysfunction, should lead to the development of new and improved therapies for a wide range of diseases.