Mitochondria- Definition, Structure, Functions and Diagram

Mitochondria are tiny organelles that are found in almost all eukaryotic cells, from plants to animals to fungi. They are often called the "powerhouses" of the cell because they produce most of the energy that the cell needs to function. Mitochondria use oxygen and nutrients from food to create a molecule called adenosine triphosphate (ATP), which is the main source of chemical energy for cellular processes. Without mitochondria, most cells would not be able to survive.

Mitochondria are also involved in many other important functions besides energy production. For example, mitochondria help regulate the levels of calcium ions in the cell, which are essential for signaling and muscle contraction. Mitochondria also produce some hormones and enzymes that are involved in metabolism and detoxification. Mitochondria can also trigger a process called apoptosis, or programmed cell death, which is important for eliminating damaged or unwanted cells.

Mitochondria are unique among organelles because they have their own DNA and ribosomes, which allow them to make some of their own proteins. Mitochondria are thought to have evolved from ancient bacteria that were engulfed by larger cells and formed a symbiotic relationship with them. This is why mitochondria have a double-membrane structure and resemble bacteria in size and shape. Mitochondria can also divide independently of the cell cycle, which means they can increase or decrease their number depending on the energy demands of the cell.

Mitochondria are essential for life as we know it. They play a key role in cellular respiration, which is the process of converting food into usable energy. They also participate in many other cellular functions that are vital for growth, development, and survival. Mitochondria are fascinating organelles that reveal a lot about the evolution and diversity of life on Earth. In this article, we will explore the structure, functions, and diagram of mitochondria in more detail.

• Mitochondria were first observed by the Swiss physiologist Albert von Kolliker in 1857, who described them as "granules" in the muscle cells of insects .
• In 1890, the German scientist Richard Altmann developed a new method of staining tissues with acid fuchsin, which allowed him to see the mitochondria more clearly. He called them "bioblasts" and proposed that they were fundamental units of life .
• In 1898, another German scientist, Carl Benda, used a different stain, crystal violet, to study the mitochondria. He noticed that they sometimes appeared as threads and sometimes as granules. He coined the term "mitochondrion", from the Greek words for thread (mitos) and granule (chondros) .
• In 1900, the German biochemist Leonor Michaelis demonstrated that mitochondria could be stained with Janus green, a dye that is taken up by living cells. This proved that mitochondria were not artifacts of tissue preparation, but real structures within the cells .

Mitochondria are double-membrane organelles that have a complex and dynamic structure. They consist of four distinct domains: the outer membrane, the inner membrane, the intermembrane space, and the matrix. Each domain has a specific function and composition that contributes to the overall role of mitochondria in cellular metabolism and signaling.

Outer Membrane

The outer membrane is the smooth and continuous membrane that surrounds the mitochondrion. It is composed of a phospholipid bilayer with embedded proteins, such as porins, which allow the passage of small molecules (up to 10 kDa) between the cytosol and the intermembrane space. The outer membrane also contains receptors and transporters for importing proteins and other molecules into the mitochondria.

Inner Membrane

The inner membrane is the highly folded and convoluted membrane that encloses the mitochondrial matrix. It is also composed of a phospholipid bilayer with embedded proteins, but it has a different lipid composition and protein-to-lipid ratio than the outer membrane. The inner membrane contains many enzymes and complexes of the electron transport chain (ETC), which are responsible for generating ATP through oxidative phosphorylation. The inner membrane also contains proton pumps that create an electrochemical gradient across the membrane, which drives ATP synthesis by ATP synthase. The inner membrane forms numerous infoldings called cristae, which increase the surface area for ETC and ATP synthesis. The shape and number of cristae can vary depending on the metabolic state and activity of the mitochondria.

Intermembrane Space

The intermembrane space is the narrow space between the outer and inner membranes. It has a similar composition to the cytosol, except for a lower pH and a higher concentration of proteins. Some of these proteins are involved in transporting electrons from the cytosol to the ETC, such as cytochrome c and ubiquinone. Some of these proteins are also involved in regulating apoptosis, such as cytochrome c and pro-apoptotic factors.

Matrix

The matrix is the aqueous compartment enclosed by the inner membrane. It contains a high concentration of soluble enzymes, coenzymes, metabolites, ions, and molecules that are involved in various metabolic pathways. One of these pathways is the citric acid cycle (also known as the Krebs cycle or the tricarboxylic acid cycle), which oxidizes acetyl-CoA derived from glycolysis or fatty acid oxidation to produce CO2, NADH, FADH2, and GTP. The matrix also contains mitochondrial DNA (mtDNA), which encodes for some of the proteins of the ETC and ATP synthase, as well as mitochondrial ribosomes (mitoribosomes), which synthesize these proteins. Mitochondria are semi-autonomous organelles that can replicate their own DNA and ribosomes independently of the nuclear DNA and ribosomes.

The outer mitochondrial membrane (OMM) is the smooth and continuous membrane that surrounds the mitochondria. It has a thickness of about 6-7 nm and a phospholipid composition similar to that of the plasma membrane. The OMM contains about 50% protein and 50% lipid by mass.

The main function of the OMM is to regulate the passage of molecules and ions into and out of the mitochondria. The OMM is permeable to small molecules (less than 5000 Da) and ions, such as water, oxygen, carbon dioxide, ATP, ADP, phosphate, pyruvate, and other metabolites. This allows the exchange of substrates and products between the cytosol and the intermembrane space (IMS), which is the region between the OMM and the inner mitochondrial membrane (IMM).

The OMM also contains specific transport proteins that facilitate the movement of larger molecules and macromolecules across the membrane. These include:

• Porins: These are large channel-forming proteins that span the OMM and allow the diffusion of molecules up to 10 kDa in size. The most abundant porin in the OMM is called voltage-dependent anion channel (VDAC), which is involved in regulating the flux of metabolites and ions across the OMM. VDAC also interacts with other proteins on both sides of the OMM, such as hexokinase, Bcl-2 family proteins, and cytochrome c. These interactions modulate the functions of VDAC in energy metabolism, apoptosis, and oxidative stress.
• Translocases: These are protein complexes that mediate the import and export of specific macromolecules across the OMM. The most important translocase in the OMM is called translocase of the outer membrane (TOM), which is responsible for importing most of the proteins that are synthesized in the cytosol and destined for the mitochondria. TOM consists of several subunits that recognize different types of mitochondrial targeting signals on the precursor proteins. TOM also cooperates with other translocases in the IMM and the matrix to facilitate the translocation of proteins across both membranes.
• Receptors: These are proteins that bind to specific ligands or signals on the surface of the OMM and trigger various cellular responses. For example, mitochondrial calcium uniporter (MCU) is a receptor that senses calcium ions in the cytosol and transports them into the matrix through a channel in the IMM. Calcium ions play a crucial role in regulating various mitochondrial functions, such as energy production, heat generation, hormone synthesis, and apoptosis.

The OMM also serves as a platform for various enzymatic reactions and protein-protein interactions that are essential for mitochondrial function and communication with other cellular organelles. Some examples are:

• Fatty acid oxidation: The OMM contains several enzymes that catalyze the first step of fatty acid oxidation, which is the conversion of fatty acids into fatty acyl-CoA molecules. These molecules can then cross the OMM through carnitine palmitoyltransferase I (CPT I) and enter the matrix for further oxidation.
• Phospholipid synthesis: The OMM contains enzymes that synthesize phospholipids from glycerol-3-phosphate and fatty acyl-CoA molecules. These phospholipids are important for maintaining the structure and function of mitochondrial membranes.
• Mitochondria-associated membranes (MAMs): These are regions of close contact between the OMM and the endoplasmic reticulum (ER) membrane. MAMs facilitate the exchange of lipids, calcium ions, and other molecules between these two organelles. MAMs also play a role in regulating mitochondrial dynamics, autophagy, inflammation, and apoptosis.

In summary, the outer mitochondrial membrane is a multifunctional membrane that controls the entry and exit of molecules and ions into and out of the mitochondria. It also participates in various metabolic pathways and inter-organelle interactions that are vital for mitochondrial function.

The inner mitochondrial membrane (IMM) is the membrane that separates the mitochondrial matrix from the intermembrane space. The IMM has a complex structure and composition, and it is responsible for most of the metabolic functions of mitochondria.

The IMM is extensively folded and compartmentalized, forming invaginations called cristae that increase the surface area of the membrane. The cristae are connected to the inner boundary membrane, which is adjacent to the outer membrane, by narrow junctions. The number and shape of cristae vary depending on the cell type and metabolic state.

The IMM is rich in proteins, accounting for about 80% of its mass. The proteins include many enzymes, coenzymes, and other components of the electron transport chain (ETC), which is the main pathway for oxidative phosphorylation and ATP synthesis in mitochondria. The ETC consists of four protein complexes (I-IV) and two mobile electron carriers (coenzyme Q and cytochrome c) that transfer electrons from reduced substrates (such as NADH and FADH2) to oxygen, generating a proton gradient across the IMM. The proton gradient drives the ATP synthase (complex V), a rotary enzyme that converts ADP and phosphate into ATP.

The IMM also contains many transporters and channels that regulate the exchange of metabolites, ions, and signals between the matrix and the intermembrane space or the cytosol. For example, the IMM has permeases for citrate, malate, pyruvate, glutamate, aspartate, and other intermediates of the Krebs cycle and amino acid metabolism; antiporters for ADP/ATP and phosphate; uniporters for calcium; and pores for potassium. The IMM is impermeable to most small molecules, except for oxygen, carbon dioxide, and water.

The IMM plays a crucial role in maintaining the mitochondrial function and integrity. The IMM is involved in regulating the mitochondrial membrane potential, which is essential for ATP production, ion homeostasis, reactive oxygen species (ROS) generation, and apoptosis. The IMM also participates in mitochondrial biogenesis, fusion, fission, and quality control processes that modulate the number, shape, size, and activity of mitochondria according to cellular needs.

The intermembrane space is the region between the outer and inner mitochondrial membranes. It has a similar composition to the cytosol of the cell, except for the protein content. The intermembrane space contains several proteins that are involved in different functions of the mitochondria.

One of the main functions of the intermembrane space is to facilitate the transport of protons (H+) across the inner membrane during oxidative phosphorylation. The electron transport chain in the inner membrane pumps protons from the matrix to the intermembrane space, creating a proton gradient that drives the synthesis of ATP by ATP synthase. The intermembrane space also contains a protein called cytochrome c, which transfers electrons from complex III to complex IV of the electron transport chain.

Another function of the intermembrane space is to participate in the import of proteins into the mitochondria. Most mitochondrial proteins are encoded by nuclear genes and synthesized in the cytosol. They are then transported into the mitochondria by specific translocases in the outer and inner membranes. Some proteins are targeted to the intermembrane space by a signal sequence that is cleaved off by a protease in the outer membrane. Other proteins are imported into the matrix and then translocated to the intermembrane space by another protease in the inner membrane.

A third function of the intermembrane space is to regulate apoptosis or programmed cell death. Apoptosis is a process that eliminates unwanted or damaged cells in a controlled manner. It is triggered by various signals, such as DNA damage, oxidative stress, or growth factor deprivation. Some of these signals activate proteins called Bcl-2 family members, which can either promote or inhibit apoptosis. Some pro-apoptotic Bcl-2 proteins, such as Bax and Bak, form pores in the outer membrane and release cytochrome c and other proteins from the intermembrane space into the cytosol. These proteins then activate caspases, which are enzymes that cleave other proteins and cause cell death.

The intermembrane space is therefore an important compartment of the mitochondria that performs various functions related to energy production, protein import, and apoptosis. It has a distinct composition and protein content that reflect its roles in these processes.

The mitochondrial matrix is the space within the inner membrane of the mitochondria. It is viscous and contains various molecules and structures that are essential for the mitochondrial functions. Some of the components of the mitochondrial matrix are:

• Mitochondrial DNA (mtDNA): This is a circular, double-stranded DNA molecule that encodes some of the proteins and RNAs involved in mitochondrial protein synthesis and oxidative phosphorylation. Mitochondria have their own ribosomes (mitoribosomes) and tRNAs that are also located in the matrix. Mitochondria can replicate their DNA independently of the nuclear DNA, and they are inherited maternally in most organisms.

• Soluble enzymes: The matrix contains many enzymes that catalyze various metabolic reactions, such as:

  • The Krebs cycle (or citric acid cycle): This is a series of reactions that oxidize acetyl-CoA, derived from pyruvate or fatty acids, to produce carbon dioxide, reduced coenzymes (NADH and FADH2), and ATP. The Krebs cycle is the central pathway of cellular respiration, and it connects glycolysis, fatty acid oxidation, amino acid catabolism, and oxidative phosphorylation. Some of the enzymes involved in the Krebs cycle are pyruvate dehydrogenase, citrate synthase, aconitase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinyl-CoA synthetase, fumarase, and malate dehydrogenase.

  • The urea cycle: This is a cycle of reactions that convert ammonia, a toxic byproduct of amino acid breakdown, into urea, which can be excreted by the kidneys. The urea cycle involves four enzymes: ornithine transcarbamylase, argininosuccinate synthetase, argininosuccinate lyase, and arginase. The urea cycle also requires aspartate and fumarate as intermediates that link it to the Krebs cycle.

  • The fatty acid synthesis: This is a process that synthesizes fatty acids from acetyl-CoA and malonyl-CoA. Fatty acids are important components of phospholipids, triglycerides, and other biomolecules. The fatty acid synthesis requires an enzyme complex called fatty acid synthase, which consists of multiple catalytic domains that perform different reactions. Fatty acid synthesis occurs in the cytoplasm of most cells, but in plants and some algae, it takes place in the mitochondrial matrix.

• Nucleotide cofactors and inorganic ions: The matrix also contains various molecules that are required for the enzymatic reactions or for the regulation of mitochondrial functions. Some examples are:

  • Coenzyme A (CoA): This is a coenzyme that carries acyl groups (such as acetyl or fatty acyl) in various metabolic pathways. CoA is derived from pantothenic acid (vitamin B5) and adenosine triphosphate (ATP). CoA is essential for the pyruvate dehydrogenase complex, the Krebs cycle, fatty acid oxidation, fatty acid synthesis, and other reactions.

  • Nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD): These are coenzymes that act as electron carriers in oxidative phosphorylation and other redox reactions. NAD+ and FAD accept electrons from reduced substrates (such as NADH and FADH2) and transfer them to the electron transport chain in the inner mitochondrial membrane. NAD+ is derived from niacin (vitamin B3) and FAD is derived from riboflavin (vitamin B2).

  • Calcium ions (Ca2+): These are important signaling molecules that regulate various cellular processes, such as muscle contraction, neurotransmitter release, gene expression, and apoptosis. Ca2+ can enter or exit the mitochondrial matrix through specific transporters or channels in the inner mitochondrial membrane. The mitochondrial Ca2+ uptake can modulate the activity of some enzymes in the matrix, such as pyruvate dehydrogenase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, and ATP synthase. The mitochondrial Ca2+ release can trigger apoptosis or necrosis by activating caspases or opening the mitochondrial permeability transition pore.

The mitochondrial matrix has a pH of about 7.8, which is higher than the pH of the intermembrane space (about 7.0-7.4). This pH gradient is maintained by the proton pumps in the inner mitochondrial membrane that pump protons out of the matrix during oxidative phosphorylation. The pH gradient is important for driving ATP synthesis by ATP synthase and for regulating some transport processes across the inner mitochondrial membrane.

The mitochondrial matrix plays a crucial role in cellular energy metabolism and homeostasis. It contains many molecules and structures that enable mitochondria to perform their functions efficiently and adapt to different conditions.

Mitochondria are semi-autonomous organelles, meaning that they have some degree of independence from the rest of the cell. They have their own genetic system, consisting of circular and double-stranded DNA molecules called mtDNA . MtDNA encodes for 13 proteins that are essential for oxidative phosphorylation, as well as 22 tRNAs and 2 rRNAs that are involved in mitochondrial protein translation.

Mitochondria also have their own ribosomes, called mitoribosomes, that are responsible for synthesizing the proteins encoded by mtDNA . Mitoribosomes are composed of two subunits: a large subunit (39S) and a small subunit (28S), which together form a 55S ribosome. Mitoribosomes differ from cytoplasmic ribosomes in their structure, composition, and sensitivity to antibiotics .

The ability of mitochondria to replicate, transcribe, and translate their own DNA makes them semi-autonomous organelles. However, they are not completely independent from the nuclear genome, as most of the proteins required for mitochondrial function are encoded by nuclear genes and imported into the mitochondria . Therefore, there is a complex interplay between the nuclear and mitochondrial genomes that ensures the proper regulation and coordination of mitochondrial biogenesis and activity .

Mitochondria are essential for the survival and function of almost all eukaryotic cells. They perform a variety of tasks that contribute to cellular metabolism, signaling, and homeostasis. Some of the main functions of mitochondria are:

• Energy production: Mitochondria are the sites of aerobic respiration, which converts nutrients such as glucose and fatty acids into adenosine triphosphate (ATP), the main energy currency of the cell. ATP is used to power many biochemical reactions and cellular processes, such as muscle contraction, nerve transmission, and biosynthesis . Mitochondria produce ATP by a series of reactions known as the tricarboxylic acid (TCA) cycle, the electron transport chain (ETC), and oxidative phosphorylation .
• Heat production: Mitochondria can generate heat by uncoupling the ETC from oxidative phosphorylation. This means that the protons that are pumped across the inner mitochondrial membrane by the ETC do not return to the matrix through ATP synthase, but through a protein called uncoupling protein 1 (UCP1). This process dissipates the proton gradient as heat, rather than using it to make ATP. Heat production by mitochondria is important for thermoregulation in mammals, especially in brown adipose tissue (BAT), which contains a high density of mitochondria with UCP1.
• Calcium ion regulation: Mitochondria can take up and release calcium ions (Ca2+) from and into the cytosol, acting as buffers and modulators of intracellular Ca2+ levels. Ca2+ is an important second messenger that mediates various cellular responses, such as muscle contraction, neurotransmitter release, gene expression, and apoptosis. Mitochondria can sense changes in cytosolic Ca2+ and adjust their metabolism accordingly. For example, increased Ca2+ uptake by mitochondria can stimulate the TCA cycle and ATP production.
• Hormone production: Mitochondria are involved in the synthesis of some hormones, such as steroid hormones and thyroid hormones. Steroid hormones are derived from cholesterol, which is converted into pregnenolone by an enzyme located in the inner mitochondrial membrane. Pregnenolone then serves as a precursor for other steroid hormones, such as cortisol, aldosterone, testosterone, and estrogen. Thyroid hormones are derived from tyrosine, which is iodinated and coupled by enzymes located in the mitochondrial matrix of thyroid follicular cells. The resulting thyroid hormones, triiodothyronine (T3) and thyroxine (T4), regulate metabolism, growth, and development.
• Detoxification: Mitochondria can detoxify some toxic substances by using enzymes such as cytochrome P450 and glutathione S-transferase. These enzymes can oxidize or conjugate xenobiotics (foreign chemicals) and make them more water-soluble and easier to excrete. Mitochondria are especially abundant in liver cells, which play a major role in detoxification of drugs, alcohol, and other harmful compounds.
• Apoptosis: Mitochondria can trigger programmed cell death or apoptosis when the cell is damaged or stressed beyond repair. Apoptosis is a controlled process that eliminates unwanted or harmful cells without causing inflammation or tissue damage. Mitochondria can initiate apoptosis by releasing pro-apoptotic factors such as cytochrome c, apoptosis-inducing factor (AIF), and second mitochondria-derived activator of caspases (SMAC) into the cytosol. These factors activate caspases, which are proteases that cleave various cellular proteins and lead to cell death.

Mitochondria are multifunctional organelles that play a vital role in cellular physiology and pathology. Dysfunction or damage of mitochondria can impair their functions and cause various diseases, such as neurodegenerative disorders, metabolic disorders, cardiovascular diseases, cancer, and aging.

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