mitochondria

(cell and molecular biology) Minute cytoplasmic organelles in the form of spherical granules, short rods, or long filaments found in almost all living cells; submicroscopic structure consists of an external membrane system.

Specialized organelles of all eukaryotic cells that use oxygen (see illustration). Often called the powerhouses of the cell, mitochondria are responsible for energy generation by the process of oxidative phosphorylation. In this process, electrons produced during the oxidation of simple organic compounds are passed along a chain of four membrane-bound enzymes (the electron transport or respiratory chain), finally reacting with and reducing molecular oxygen to water. The movement of the electrons releases energy that is used to build a gradient of protons across the membrane in which the electron transport chain is situated. Like a stream of water that drives the turbines in a hydroelectric plant, these protons flow back through adenosine triphosphate (ATP) synthase, a membrane-bound enzyme that acts as a molecular turbine. Rotation of part of ATP synthase results in storage of energy in the form of ATP, the universal energy currency of the cell.

Electron micrograph of a thin section through the pancreas of a bat, showing a typical mitochondrion in profile. Note how the cristae are formed by extensive folding of the inner membrane. (Courtesy of K. R. Porter)

Besides their role in energy generation, mitochondria house numerous enzymes that carry out steps essential to metabolism. Defects in mitochondrial assembly or function generally have serious consequences for survival of the cell. In humans, mitochondrial dysfunction is the underlying cause of a wide range of degenerative diseases, with energy-demanding cells such as those of the central nervous and endocrine systems, heart, muscle, and kidney being most severely affected.

Mitochondria are bounded by two concentric membranes referred to as the outer and the inner. This creates two distinct compartments, the matrix and the intermembrane space. The outer membrane consists of a bilayer containing about 80% lipid. It is freely permeable to molecules smaller than about 5000 daltons. The inner membrane is also a lipid bilayer. It is extremely rich in protein (about 75%) and is impermeable to even the smallest of ions. The inner membrane contains the enzymes of the electron transport chain and the ATP synthase, together with a set of transporter proteins that regulate the movement of metabolites in and out of the matrix space. Mitochondria of cells that depend on a high level of ATP production are usually extensively folded to produce structures called cristae (see illustration). These greatly increase the surface area of the inner membrane, allowing many more copies of the enzymes of oxidative phosphorylation.

The intermembrane space contains enzymes capable of using some of the ATP that is transported out of the matrix to phosphorylate other nucleotides. The matrix space is packed with a hundred or so water-soluble proteins that form a sort of semisolid gel. They include enzymes of the tricarboxylic acid (Krebs) cycle and enzymes required for the oxidation of pyruvate and fatty acids, comprising steps in the biosynthesis or degradation of amino acids, nucleotides, and steroids.

Both mitochondria and chloroplasts contain DNA and the machinery necessary to express the information stored there. In both cases, the DNAs are relatively small and simple compared with DNA in the nucleus. While chloroplast DNA tends to be very similar in size in all organisms examined, mtDNA varies widely in complexity, from 16–18 kilobases in metazoa to upward of 2000 kilobases in some higher plants. In the case of higher-plant mtDNAs, some extra sequences appear to have been picked up from chloroplast and nuclear DNAs. MtDNA is generally circular, although some linear exceptions are known among the yeasts, algae, and protozoa.

The information content of most mtDNA is limited. This means that most of the several hundred proteins found in these organelles are encoded by genes located in nuclear DNA. These proteins are synthesized in the cytosol and subsequently transported specifically to the respective organelles. The contributions of the two genetic systems are usually closely coordinated, so that cells synthesize organelles of more or less constant composition.

Many organisms, including humans, show uniparental inheritance of mitochondrial genes because one parent contributes more cytoplasm to the zygote than the other. In humans, it is the egg cell provided by the mother that contributes the cytoplasm. Human mitochondrial genes are thus inherited maternally.

Recent years have seen a growing interest in human diseases that result from mitochondrial dysfunction. A number of these result from mutations in mtDNA. Others are linked to nuclear genes, whose mutation disturbs oxidative phosphorylation or impairs mitochondrial assembly. Mutations in mtDNA are remarkably frequent and lead to a wide range of degenerative, mainly neuromuscular diseases. Most of these diseases are maternally inherited, but some appear to be spontaneous, possibly resulting from error-prone replication of mtDNA. A striking feature of mtDNA-related diseases is the enormous diversity in clinical presentation. This diversity is attributable to two main factors: (1) Heterogeneity in the mtDNA population. Most human tissues contain many thousands of mtDNA molecules per cell. The severity of clinical symptoms depends on the number of mutated molecules present. (2) Dependence of a particular cell type on mitochondrial function (mainly ATP production). Cells with a high requirement for mitochondrially generated ATP are more severely affected than cells with alternative sources of ATP.

Besides their role in metabolism and energy-linked processes, mitochondria have recently been identified as important players in the initiation of apoptosis (programmed cell death). On one hand, the mitochondrial outer membrane houses a number of members of the Bcl-2 family of apoptosis regulatory proteins. On the other hand, release of certain mitochondrial proteins from the intermembrane space is instrumental in activating specialized proteases called caspases. These catalyze a degradative cascade in the cytoplasm that eventually ends in cell death.

Mammalian mtDNAs accumulate mutations at high rates and evolve correspondingly fast (up to 12–15 times faster than single-copy genes in nuclear DNA and up to 100 times faster for rRNA and tRNA genes). This behavior reflects both a high incidence of mutations and a high probability of their fixation. The first is probably related to oxidative damage to mtDNA by oxygen free radicals produced as by-products of electron transfer through the respiratory chain. The second has been attributed to the lack of efficient DNA repair (mitochondria lack nucleotide-excision repair) and to a relatively high tolerance of many mitochondrial gene products to mutational change.

The rapid rate of sequence evolution of mammalian mtDNAs makes these genomes highly sensitive indicators of recent evolutionary relationships. Unlike their nuclear counterparts, mtDNAs do not undergo recombination during sexual transmission and are strictly maternally inherited. Sequence changes in mtDNA therefore provide a clear record of the history of the female lineages through which this DNA has been transmitted.

Small, rodlike, threadlike, or granular organelles within the cytoplasm that function in cellular metabolism and respiration and occur in varying numbers in all living cells except bacteria, viruses, blue-green algae, and mature erythrocytes.

Energy-producing cell organelle.

[Gr.] plural of mitochondrion; small, spherical to rod-shaped, membrane-bounded cytoplasmic organelles that are the principal sites of ATP synthesis; they also contain enzymes of the citric acid cycle and for fatty acid oxidation, oxidative phosphorylation, and other biochemical pathways. Mitochondria also contain DNA, RNA and ribosomes; they replicate independently and synthesize some of their own proteins.