Mitochondrial DNA


Mitochondrial DNA, or mtDNA, is the deoxyribonucleic acid that resides inside the mitochondria, ie the organelles of eukaryotic cells responsible for the very important cellular process of oxidative phosphorylation.

Mitochondrial DNA has some similarities with nuclear DNA, such as the double strand of nucleotides, the composition in terms of nitrogenous bases, the presence of genes, etc.

However, it also has some peculiarities, both structural and functional, which make it unique in its kind. These features include: the circularity of the double strand of nucleotides, the content of genes (which is only 37 elements) and the almost total absence of non-coding nucleotide sequences.

Mitochondrial DNA plays a fundamental role in cell survival: it produces the enzymes necessary for the realization of oxidative phosphorylation.

What is mitochondrial DNA?

Mitochondrial DNA, or mtDNA, is the DNA located inside the mitochondria .

Mitochondria are those large cellular organelles, typical of eukaryotic organisms, which convert the chemical energy contained in food into ATP, which is a form of energy that can be used by cells.


Of tubular, filamentous or granular form, the mitochondria reside in the cytoplasm, occupying almost 25% of the volume of the latter.

They have two phospholipid bilayer membranes, one more external and one more internal.

The outermost membrane, known as the outer mitochondrial membrane, represents the perimeter of each mitochondria and has transport proteins (porine and not only), which make it permeable to molecules of size equal to or less than 5, 000 daltons.

The innermost membrane, known as the inner mitochondrial membrane, contains all the enzymatic components (or enzymes) and coenzyme components necessary for ATP synthesis, and delimits a central space, called a matrix .

Unlike the outermost membrane, the inner mitochondrial membrane has numerous invaginations - the so-called crests - that increase its total area.

Between the two mitochondrial membranes, there is a space of almost 60-80 Angstroms (A). This space is called intermembrane space . The intermembrane space has a composition very similar to that of the cytoplasm.

The synthesis of ATP, operated by the mitochondria, is a very complex process, which biologists identify with the term oxidative phosphorylation .


Figure: a human mitochondria.

Mitochondrial DNA resides in the mitochondria matrix, ie in the space delimited by the inner mitochondrial membrane.

Based on reliable scientific studies, each mitochondria can contain from 2 to 12 copies of mitochondrial DNA.

Considering the fact that, in the human body, some cells can contain within them several thousand mitochondria, the total number of mitochondrial DNA copies, in a single human cell, can even reach 20, 000 units.

Note: the number of mitochondria in human cells varies depending on the cell type. For example, hepatocytes (ie liver cells) can contain between 1, 000 and 2, 000 mitochondria each, while erythrocytes (ie red blood cells) are totally devoid of them.


The general structure of a mitochondrial DNA molecule resembles the general structure of nuclear DNA, that is the genetic heritage present within the nucleus of eukaryotic cells.

In fact, similarly to nuclear DNA:

  • Mitochondrial DNA is a biopolymer, consisting of two long strands of nucleotides . Nucleotides are organic molecules, resulting from the union of three elements: a sugar with 5 carbon atoms (in the case of DNA, deoxyribose ), a nitrogenous base and a phosphate group .
  • Each nucleotide of the mitochondrial DNA binds to the next nucleotide of the same filament, by means of a phosphodiester bond between the carbon 3 of its deoxyribose and the immediately following nucleotide phosphate group.
  • The two strands of mitochondrial DNA have opposite orientation, with the head of one interacting with the end of the other and vice versa. This particular arrangement is known as an antiparallel arrangement (or antiparallel orientation ).
  • The two filaments of the mitochondrial DNA interact with each other, via the nitrogenous bases .

    Specifically, each nitrogenous base of each filament establishes hydrogen bonds with one and only one nitrogenous base, present on the other filament.

    This type of interaction is called "pairing between nitrogenous bases" or "pair of nitrogenous bases".

  • The nitrogenous bases of mitochondrial DNA are adenine, thymine, cytosine and guanine .

    The pairing to which these nitrogenous bases give rise are not random, but highly specific: adenine interacts only with thymine, while cytosine only with guanine.

  • Mitochondrial DNA is home to genes (or gene sequences). Genes are sequences of more or less long nucleotides, with a well-defined biological meaning. In most cases, they give rise to proteins.


Beyond the aforementioned analogies, human mitochondrial DNA has some structural peculiarities that distinguish it considerably from human nuclear DNA.

First, it is a circular molecule, while nuclear DNA is a linear molecule.

Thus, it has 16, 569 pairs of nitrogenous bases, while the nuclear DNA possesses the beauty of 3.3 billion.

It contains 37 genes, while nuclear DNA appears to contain between 20, 000 and 25, 000.

It is not organized in chromosomes, while nuclear DNA is divided into as many as 23 chromosomes and forms, with some specific proteins, a substance called chromatin.

Finally, it includes a series of nucleotides that participate in two genes simultaneously, while nuclear DNA has genes whose nucleotide sequences are well defined and distinct from each other.


Mitochondrial DNA is very likely to have a bacterial origin .

Indeed, based on numerous independent studies, molecular biologists believe that the cellular presence of mitochondrial DNA is the result of the incorporation, by ancestral eukaryotic cells, of independent bacterial organisms, very similar to mitochondria.

This curious discovery has only partially amazed the scientific community, as the DNA present in bacteria is generally a filament of circular nucleotides, such as mitochondrial DNA.

The theory that mitochondria and mitochondrial DNA would have a bacterial origin is called " endosymbiotic theory ", from the word " endosymbiosis ". Briefly, in biology, the term "endosymbiosis" indicates a collaboration between two organisms, which involves the incorporation of one inside the other, in order to gain a certain advantage.


According to reliable scientific studies, during the course of evolution many bacterial genes, present on the future mitochondrial DNA, would have changed location, moving into nuclear DNA.

In other words, at the beginning of endosymbiosis, some genes present now on nuclear DNA resided in the DNA of those bacterial organisms, which would then become mitochondria.

The theory that certain genes derive from mitochondrial DNA, in some species, and from nuclear DNA, in others, corroborates the theory of a gene shift between mitochondrial DNA and nuclear DNA.


Mitochondrial DNA produces enzymes (ie proteins), necessary for the correct realization of the delicate process of oxidative phosphorylation.

The instructions for the synthesis of these enzymes reside in the 37 genes that make up the genome of mitochondrial DNA.


The 37 genes of mitochondrial DNA encode for: proteins, tRNA and rRNA.

In particular:

  • 13 code for 13 proteins responsible for carrying out oxidative phosphorylation
  • 22 encode 22 molecules of tRNA
  • 2 encode 2 molecules of rRNA

The tRNA and rRNA molecules are fundamental to the synthesis of the above 13 proteins, as they make up the machinery that regulates their production.

So, in other words, the mitochondrial DNA has the information to produce a certain set of proteins and the tools necessary for the synthesis of the latter.

What are RNA, tRNA and rRNA?

RNA, or ribonucleic acid, is the nucleic acid that plays a fundamental role in the generation of proteins, starting from DNA.

Generally single-stranded, RNA can exist in various forms (or types), depending on the specific function to which it is a deputy.

TRNA and rRNA are two of these possible forms.

TRNA is used for the addition of amino acids, during the process of creating proteins. Amino acids are the molecular units that make up proteins.

The rRNA forms the ribosomes, ie the cellular structures in which protein synthesis is based.

To learn more about RNA and its functions, readers can click here.


From a functional point of view, mitochondrial DNA has some peculiar characteristics that clearly distinguish it from nuclear DNA.

Here are what these particular features consist of:

  • Mitochondrial DNA is semi-independent in the sense that it needs the intervention of some proteins synthesized from nuclear DNA.

    By contrast, nuclear DNA is completely autonomous and produces everything it needs to perform its tasks properly.

  • Mitochondrial DNA has a genetic code slightly different from that of nuclear DNA . This leads to a series of differences in the realization of proteins: if a certain sequence of nucleotides in the nuclear DNA leads to the creation of a certain protein, the same sequence in the mitochondrial DNA leads to the formation of a slightly different protein.
  • Mitochondrial DNA has very few non-coding nucleotide sequences, that is, that do not produce any protein, tRNA or rRNA. In percentage terms, only 3% of mitochondrial DNA is non-coding.

    In contrast, nuclear DNA is coding for only 7%, so it contains a large number of non-coding nucleotide sequences (93%).

Table: summary of the differences between human mitochondrial DNA and human nuclear DNA.

Mitochondrial DNA

Nuclear DNA

  • It is circular
  • It's linear
  • It has a total of 16, 569 pairs of nitrogen bases
  • It has a total of 3.3 billion pairs of nitrogenous bases
  • It contains a total of 37 genes
  • It contains between 20, 000 and 25, 000 genes
  • To function properly it needs the support of some gene products, deriving from nuclear DNA
  • It is autonomous and produces everything it needs to perform its functions properly
  • It may be present in several copies within each individual mitochondria
  • It is unique, that is, it is in one copy only, and resides in the nucleus
  • 97% of the nucleotide sequence of which it is composed is coding
  • Only 7% of the sequence of nucleotides that compose it is coding
  • It is not organized in chromosomes
  • It is divided into 23 chromosomes
  • Use a genetic code that is slightly different from the "traditional" one
  • Use the "traditional" genetic code
  • Its inheritance is maternal
  • Its inheritance is half maternal and half paternal
  • Some of its nucleotides participate in two genes simultaneously
  • The nucleotide sequences that make up the genes are well distinguished from each other


The inheritance of mitochondrial DNA is strictly maternal .

This means that, in a couple of parents, it is the woman who transmits mitochondrial DNA to the offspring (ie the children).

In a completely opposite way to the above, the inheritance of nuclear DNA is, half, maternal and half paternal. In other words, both parents contribute equally to the transmission of nuclear DNA in the progeny.

Note: the maternal inheritance of mitochondrial DNA also involves the mitochondrial structure. Thus, the mitochondria present in an individual are on a maternal mold.

Associated pathologies

Premise: a genetic mutation is a permanent change in the sequence of nucleotides, which constitute a nuclear or mitochondrial DNA gene.

Generally, the presence of a genetic mutation leads to an alteration or loss of the normal function of the gene involved.

The presence of mutations at the level of mitochondrial DNA genes can determine a wide range of diseases, including:

  • Leber's hereditary optic neuropathy
  • Kearns-Sayre syndrome
  • Leigh syndrome
  • Cytochrome C oxidase deficiency
  • Progressive external ophthalmoplegia
  • Pearson's syndrome
  • Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS syndrome)
  • Diabetes with maternal transmission deafness
  • Myoclonic epilepsy with irregular red fibers

With regard to the pathological conditions linked to one or more mitochondrial DNA mutations, two aspects must be specified.

First, the severity of the morbid state depends on the quantitative relationship between mutated mitochondrial DNA and healthy, normal mitochondrial DNA. If the number of mutated mitochondrial DNA is much higher than that of healthy DNA, the resulting condition will be more severe.

Secondly, mutations in mitochondrial DNA affect only certain tissues in the body, particularly those that require large amounts of ATP resulting from the process of oxidative phosphorylation. This is quite understandable: the cells that have the greatest need for the function to which the mitochondrial DNA normally performs are most affected by a malfunctioning mitochondrial DNA.


Leber's hereditary optic neuropathy arises due to the mutation of as many as four mitochondrial DNA genes. These genes contain the information that leads to the synthesis of the so-called complex I (or NADH oxide-reductase), one of the various enzymes involved in the process of oxidative phosphorylation.

The manifestations of the pathology consist in a progressive degeneration of the optic nerve and in a gradual loss of vision.


Kearns-Sayre syndrome appears due to the lack of a discrete part of mitochondrial DNA (NB: the lack of a certain nucleotide sequence is called deletion ).

Sufferers of Kearns-Sayre syndrome develop ophthalmoplegia (ie total or partial paralysis of the oculomotor muscles), a form of retinopathy and abnormal heart rhythm (atrioventricular block).


Leigh syndrome arises as a result of mitochondrial DNA mutations, which may involve the ATP-synthase protein (also called the V complex) and / or some tRNAs.

Leigh syndrome is a progressive neurological disease that appears during infancy or childhood and is responsible for: developmental delay, muscle weakness, peripheral neuropathy, motor disorders, difficulty in breathing and ophthalmoplegia.


Cytochrome C oxidase deficiency appears due to the mutation of at least 3 mitochondrial DNA genes. These genes are fundamental for the correct synthesis of the cytochrome C oxidase (or complex IV) enzyme involved in the process of oxidative phosphorylation.

The typical manifestations of cytochrome C oxidase deficiency consist of: skeletal muscle dysfunction, cardiac dysfunction, renal dysfunction and liver dysfunction.


Progressive external ophthalmoplegia occurs due to the lack of a substantial number of mitochondrial DNA nucleotides (deletion)

With a progressive character (as you can guess from the name), this pathology causes a paralysis of the oculomotor muscles, with consequent ptosis and considerable visual problems.


Pearson syndrome appears following a large deletion of mitochondrial DNA, similar to progressive external ophthalmoplegia and Kearns-Sayre syndrome.

The typical manifestations of Pearson syndrome consist of: sideroblastic anemia, pancreatic dysfunctions (eg insulin-dependent diabetes), neurological deficits and muscular disorders.

In general, Pearson syndrome causes the death of the subject affected at a young age. In fact, those affected by this pathology rarely reach adulthood.


The MELAS syndrome, also known as mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes, occurs as a result of the mutation of at least 5 mitochondrial DNA genes.

These genes contribute to the synthesis of NADH oxide-reductase, or complex I, and of some tRNAs.

The MELAS syndrome involves the presence of neurological disorders, muscular disorders, unusual accumulation of lactic acid in the tissues (with all the resulting symptoms), respiratory problems, loss of control of intestinal functions, recurrent fatigue, kidney problems, heart problems, diabetes, epilepsy and lack of coordination.


According to several scientific studies, even diseases such as cyclic vomiting syndrome, retinitis pigmentosa, ataxia, Parkinson's disease and Alzheimer's disease would see mitochondrial DNA and some mutations involved.


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