Mitochondria are membrane bound organelles found in most eukaryotic cells and are major sites of aerobic energy metabolism. The singular form is mitochondrion, while mitochondria is the plural. They are commonly described as the powerhouses of cells because they generate large amounts of ATP through oxidative phosphorylation, although this phrase is an oversimplification because mitochondria perform many additional functions. A typical mitochondrion has an outer membrane, an intermembrane space, an inner membrane and an internal matrix.
The inner membrane is extensively folded into structures called cristae, increasing the membrane surface available for respiratory complexes and ATP synthase. Mitochondria are dynamic organelles that can change shape, move within cells, divide, fuse and interact with other organelles. Their importance extends to metabolism, signalling, calcium regulation, apoptosis, heat production and aspects of cellular development.
Mitochondria have an unusual evolutionary origin. The leading explanation is the endosymbiotic theory, according to which mitochondria descended from an ancestral bacterium that entered into a long term symbiotic relationship with an ancestral eukaryotic cell. Evidence includes the presence of mitochondrial DNA, bacterial like ribosomes, division by processes resembling bacterial fission, double membranes and molecular similarities between mitochondria and particular bacterial lineages.
Over evolutionary time, many genes originally associated with the ancestral endosymbiont were transferred to the host cell nucleus or lost, leaving modern mitochondria dependent on nuclear encoded proteins as well as their own genomes. Mitochondria therefore represent an evolutionary merger in which genetic and biochemical systems from different ancestral sources became integrated into a single eukaryotic cell.
Mitochondria contain their own DNA, although the mitochondrial genome is much smaller than the nuclear genome. In humans, mitochondrial DNA is a circular molecule containing genes required for particular mitochondrial proteins as well as ribosomal RNAs and transfer RNAs. Most proteins functioning in mitochondria are nevertheless encoded by nuclear DNA, synthesised in the cytoplasm and imported into mitochondria through specialised protein transport systems.
Mitochondrial DNA is present in multiple copies within each mitochondrion, and cells contain many mitochondria, so a cell can contain numerous mitochondrial genome copies. Mitochondrial inheritance has distinctive patterns because mitochondria are usually transmitted through the maternal lineage in humans, although rare exceptions and unusual inheritance patterns occur. Mutations in mitochondrial or nuclear genes can disrupt mitochondrial function and cause disease.
The inner mitochondrial membrane houses the electron transport chain and ATP synthase. Electrons derived from metabolic fuels are transferred through respiratory complexes, ultimately reducing oxygen to water. As electrons move through the electron transport chain, energy is used to pump protons from the matrix into the intermembrane space. This creates an electrochemical proton gradient across the inner membrane. ATP synthase uses the energy stored in that gradient to phosphorylate ADP and produce ATP. This process is oxidative phosphorylation. The inner membrane must remain highly organised and relatively impermeable to protons for efficient energy conversion. The folded cristae increase available membrane area and contribute to the spatial organisation of respiratory complexes and ATP synthase.
The mitochondrial matrix contains enzymes involved in several metabolic pathways, including the citric acid cycle. Acetyl CoA derived from carbohydrates, fats and proteins can enter the citric acid cycle, generating reduced electron carriers such as NADH and FADH2. These carriers donate electrons to the respiratory chain, linking nutrient oxidation to ATP production. Mitochondria also participate in fatty acid beta oxidation, which produces acetyl CoA and reduced electron carriers. Amino acid metabolism and other pathways can also involve mitochondrial reactions. Mitochondria therefore act as metabolic hubs rather than isolated ATP factories. Their functions are coordinated with the cytosol, endoplasmic reticulum, peroxisomes and other cellular compartments so that carbon, nitrogen, electrons and signalling molecules can move between pathways according to cellular requirements.
Mitochondria have important functions beyond energy metabolism. They participate in calcium handling, helping cells regulate intracellular calcium concentrations and signalling. They also contribute to programmed cell death through pathways involving mitochondrial outer membrane permeabilisation and release of factors that can activate apoptotic machinery. Mitochondria can influence production and management of reactive oxygen species, which are chemically reactive molecules generated partly as consequences of electron transport.
Controlled reactive oxygen species can participate in signalling, whereas excessive oxidative stress can damage proteins, lipids and nucleic acids. Mitochondria are also involved in heat generation in specialised tissues through processes that can dissipate the proton gradient rather than converting all of its energy into ATP. These roles make mitochondrial activity closely connected to cellular stress responses and physiological regulation.
Mitochondria are highly dynamic. They undergo fusion, in which separate mitochondrial structures merge, and fission, in which mitochondria divide. These processes influence mitochondrial distribution, quality control, morphology and metabolic capacity. Damaged mitochondria can be selectively removed through a form of autophagy called mitophagy. Cells therefore maintain mitochondrial populations through coordinated biogenesis, fusion, fission and degradation. Mitochondria also establish physical contacts with the endoplasmic reticulum and other organelles, facilitating exchange of calcium, lipids and metabolic signals. Their number and activity vary substantially between cell types. Cells with high energy demands, such as cardiac and skeletal muscle cells, generally contain abundant mitochondria, whereas specialised cells may have distinctive mitochondrial organisation suited to their particular functions.
Mitochondria are associated with numerous human diseases, but it is inaccurate to assume that every mitochondrial abnormality has the same cause or consequence. Pathogenic variants in mitochondrial DNA or nuclear genes can impair oxidative phosphorylation, mitochondrial protein production, metabolism or quality control. Because mitochondrial function is particularly important for tissues with high energy requirements, the nervous system, skeletal muscle, heart and other organs can be affected in mitochondrial disorders. Mitochondrial dysfunction can also occur as part of broader diseases and ageing processes, although the relationships can be complex and context dependent. Research into mitochondria is therefore relevant to genetics, metabolism, cell biology, neuroscience, medicine and ageing biology.
