Mitochondrial Structure, Function: Beyond Energy Production

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Mitochondria are the cell's powerhouse whose internal structure has already adapted to produce high-energy compound ATP rapidly and massively. The ultrastructure can’t be distinguished under a light microscope, only an electron microscope can clearly see them.

Outer membrane

The smooth outer membrane is 6-7 nanometers thick. Proteins and lipids each account for half in the outer membrane. Mitochondria selectively exchange substances with cytosol through it. Porins on the surface selectively open, and molecules smaller than 5000KDa can pass through, such as amino acids, ATP, and acetyl-CoA, etc. There are also proteins on the outer membrane that inhibit or activate apoptosis.

Between the outer and inner membranes, there is a 6-8 nm wide gap called intermembrane space. Its composition is close to cytosol. It is filled with metabolic intermediates and some enzymes related to respiration.

Inner membrane

It is the most unique and important structure of mitochondria. Only about 20% of its composition is lipids whose main component is phospholipids, and there is almost no cholesterol. There is also a special lipid called cardiolipin on the inner membrane. They have two more hydrocarbon tails than phospholipids, so their arrangement is tighter to reduce ions permeability, especially protons. Only small molecules without charge can penetrate them. Hence, some larger molecules or ions entering the matrix need the help of carrier proteins.

Inner membrane folds toward the central cavity of mitochondria to form protruding structures called cristae. The surface area increases by 5-10 times for biochemical reactions. In the cells with active metabolism, there are not only more mitochondria, but also more cristae. The inner membrane is embedded with a large number of enzymes related to aerobic respiration, so that approximately 80% of its components are proteins. These proteins are responsible for energy metabolism (electron transport chain and ATP synthesis) and passage of substances across inner membrane. You will observe a lot of granules about 10 nanometers apart on inner membrane under an electron microscope. They are actually ATP synthase.

Matrix

Inner membrane encloses mitochondrial matrix into a gel-like compartment, where many enzymes and substrates necessary for cellular respiration are located. This is not only the site of citric acid cycle (also called Krebs cycle), β-oxidation of fatty acids, and degradation of amino acids, but also includes some steps of urea cycle, a process that converts ammonia into urea to remove cytotoxicity. In the matrix, there are also mtDNA, RNA, and mitochondrial ribosomes for somewhat self-sufficient protein synthesis. However, most proteins are still encoded by cell nucleus and synthesized by cytosolic ribosomes. Therefore, mitochondria are also called semi-autonomous organelles.

Mitochondrial function: how does it produce energy?

Burning glucose is their main function, so they have earned the nickname "cell powerhouse." Glucose is broken down into pyruvate by anaerobic glycolysis in cytosol and completely oxidized into water and carbon dioxide in mitochondria. In the matrix, pyruvate is converted into acetyl-CoA that undergoes tricarboxylic acid cycle to release high-energy compounds ATP and NADH. Electrons contributed by NADH gradually lower their energy along the electron transport chain (respiratory chain). Meanwhile, complexes on inner membrane pump protons from matrix into intermembrane space (cristae). The pH difference across the membrane is about 1. The reduced electrical energy is stored in proton concentration gradient and electric potential difference. Finally, protons flow through ATP synthase that produces 3 ATP for every rotation. If rapid heat generation is needed, protons directly penetrate uncoupling proteins instead of ATP synthase into matrix. Just like a short-circuited battery, and all the electrochemical energy dissipates as heat. Uncoupling proteins are abundant in brown fat hibernating animals use to maintain body temperature.

Frequently Asked Questions

Other functions of mitochondria?

Besides glucose, fatty acids are also oxidized here. They are broken down into acetyl-CoA in matrix via β-oxidation. The subsequent steps are exactly the same as glucose oxidation. Recently, more and more studies have indicated that the role of mitochondria is far more than just "cell powerhouse".

They assist ER in controlling the dynamic balance of calcium ion that is the second messenger in signal transmission and metabolic regulation. Calcium ion uniporter is a highly selective ion channel on the inner membrane. Concentration gradient drives calcium ions across them unidirectionally. Negatively charged matrix also facilitates the diffusion of positively charged ions. This process typically occurs when calcium ion increases in cytoplasm, such as neurotransmitter release or muscle contraction. The leaving depends on cotransport that is powered by sodium ions flowing into mitochondria.

Tricarboxylic acid cycle or citric acid cycle also serves as a transit station for substances breakdown and synthesis. In cytoplasm, malic acid and citric acid are converted into oxaloacetate and acetyl-CoA. The former is involved in making glucose and aspartic acid (a precursor of various amino acids). Acetyl-CoA is the raw material for fatty acids. The α-Ketoglutarate also participates in amino acid metabolism. It accepts an amino group from an existing amino acid and transformed into glutamate for making other amino acids.

Mitochondria regulate metabolism. As intermediates in Krebs cycle increase, catabolism slows down and the production of glucose, amino acids, and fatty acids is promoted. Conversely, cell will accelerate the oxidation of organic matter. In addition, there are cytochrome c and other apoptosis-inducing factors in mitochondria. When apoptosis is activated, pores appear on the outer membrane to release these factors into the cytoplasm.

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