Mitochondrial Biological Functions

Mitochondria are semi-autonomous organelles in eukaryotic cells surrounded by a double layer of highly specialized unit membranes. They are the new frontier of current life science and molecular medicine research. A large number of studies have shown that mitochondria play a very important regulatory role in cell metabolism, stress and a series of life activities. Mitochondrial dysfunction involves a wide range of diseases, including diabetes, neurodegenerative diseases, septic shock, myocardial ischemia-reperfusion injury, cancer, etc. Testing the function of mitochondria is of great significance in diagnosing diseases. This article intends to provide a review on the structure, function and detection methods of mitochondria.

Biological Function

The main biological function of mitochondria is to synthesize ATP and provide energy. Approximately 95% of the energy required for cellular life activities comes from mitochondria. In addition, mitochondria also play a very important role in maintaining calcium homeostasis, regulating membrane potential, controlling apoptosis, and maintaining cellular pH balance.

• Energy Conversion

Mitochondria are the sites where eukaryotes carry out oxidative metabolism, and are where sugars, fats and amino acids are ultimately oxidized to release energy. The common pathways for final oxidation that mitochondria are responsible for are the tricarboxylic acid cycle and oxidative phosphorylation, which correspond to the second and third stages of aerobic respiration respectively.

• Tricarboxylic Acid Cycle

Each molecule of pyruvate produced during glycolysis is transported across the mitochondrial membrane by active transport. After entering the mitochondrial matrix, pyruvate will be oxidized and combined with coenzyme A to generate CO2, reduced coenzyme I and acetyl-CoA.

Acetyl-CoA is the primary substrate of the tricarboxylic acid cycle. The enzymes involved in this cycle are free in the mitochondrial matrix except for succinate dehydrogenase located in the inner mitochondrial membrane. In the tricarboxylic acid cycle, each molecule of acetyl-CoA is oxidized and produces reduced cofactors for the initial electron transport chain (including 3 molecules of NADH and 1 molecule of FADH2) and 1 molecule of guanosine triphosphate (GTP).

• Oxidative Phosphorylation

Reducing molecules such as NADH and FADH2 (the reducing equivalents in the cytoplasmic matrix can enter the electron transport chain from the malate-aspartate shuttle system composed of antiporters or through the glycerol phosphate shuttle) are in the electron transport chain After several steps of reaction, oxygen is finally reduced and energy is released, part of which is used to generate ATP, and the rest is lost as heat energy.

Enzyme complexes (NADH-ubiquinone reductase, ubiquinone-cytochrome c reductase, cytochrome c oxidase) on the inner mitochondrial membrane use the energy released during the process to pump protons into the mitochondrial intermembrane space against the concentration gradient.

Although this process is efficient, there are still a small number of electrons that prematurely reduce oxygen and form reactive oxygen species (ROS) such as superoxide. These substances can cause oxidative stress and degrade mitochondrial performance.

When protons are pumped into the mitochondrial intermembrane space, an electrochemical gradient is established on both sides of the mitochondrial inner membrane, and protons tend to diffuse along the concentration gradient. The only diffusion channel for protons is ATP synthase (respiratory chain complex V). When protons pass through the complex from the intermembrane space back to the mitochondrial matrix, the electrical potential energy is used by ATP synthase to synthesize ATP from ADP and phosphate.

• Store Calcium Ions

Mitochondria can store calcium ions and can cooperate with structures such as the endoplasmic reticulum and extracellular matrix to control the dynamic balance of calcium ion concentration in cells. The ability of mitochondria to rapidly absorb calcium ions makes them a buffer for calcium ions in the cell. Driven by the membrane potential of the inner mitochondrial membrane, calcium ions can be transported into the mitochondrial matrix by the one-way transporter present in the inner mitochondrial membrane; when excreted from the mitochondrial matrix, it requires the assistance of sodium-calcium exchange proteins or through calcium-induced calcium release (CICR) mechanism.

When calcium ions are released, it causes a "calcium wave" accompanied by a large change in membrane potential, which can activate certain second messenger system proteins and coordinate the release of neurotransmitters in synapses and the secretion of hormones in endocrine cells. Mitochondria are also involved in calcium ion signal transduction during apoptosis.

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