Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Mitochondrial Inheritance

393

•

cells, the oxidative phosphorilation occurs in the mitochon-

dria, through the chemiosmotic coupling, the process of trans-

ferring hydrogen protons (H+) from the space between the

external and the internal membrane of mitochondria to the ele-

mentary corpuscles. H+are produced in the mitochondrial

matrix by the citric acid cycle and actively transported through

the internal membrane to be stored in the inter-membrane

space, thanks to the energy released by the electrons passing

through the electron-transporting chain. The transport of H+to

the elementary corpuscles is mediated by enzymes of the

ATPase family and causes two different effects. First, 50% of

the transported H+is dissipated as heat. Second, the remaining

hydrogen cations are used to synthesize ATP from ADP

(adenosine di-phosphate) and inorganic phosphate, which is

the final step of the oxidative phosphorilation. ATP constitutes

the main source of chemical energy used by the metabolismof

eukaryotic cells in the activation of several multiple signal

transductionpathways to the nucleus, intracellular enzymatic

system activation, active transport of nutrients through the cell

membrane, and nutrient metabolization.

See alsoCell membrane transport; Krebs cycle; Mitochondrial

DNA; Mitochondrial inheritance

MMitochondrial DNAITOCHONDRIALDNA

Mitochondria are cellular organelles that generate energy in

the form of ATP through oxidative phosphorylation. Each cell

contains hundreds of these important organelles. Mitochondria

are inherited at conception from the mother through the cyto-

plasmof the egg. The mitochondria, present in all of the cells

of the body, are copies of the ones present in at conception in

the egg. When cells divide, the mitochondria that are present

are randomly distributed to the daughter cells, and the mito-

chondria themselves then replicate as the cells grow.

Although many of the mitochondrial genes necessary

for ATP production and other genes needed by the mitochon-

dria are encoded in the DNA of the chromosomesin the

nucleusof the cell, some of the genes expressed in mitochon-

dria are encoded in a small circular chromosome which is con-

tained within the mitochondrion itself. This includes 13

polypeptides, which are components of oxidative phosphory-

lation enzymes, 22 transfer RNA (t-RNA) genes, and two

genes for ribosomal RNA (r-RNA). Several copies of the

mitochondrial chromosome are found in each mitochondrion.

These chromosomes are far smaller than the chromosomes

found in the nucleus, contain far fewer genes than any of the

autosomes, replicate without going through a mitotic cycle,

and their morphological structure is more like a bacterial chro-

mosome than it is like the chromosomes found in the nucleus

of eukaryotes.

Genes which are transmitted through the mitochondrial

DNA are inherited exclusively from the mother, since few if any

mitochondria are passed along from the sperm. Genetic diseases

involving these genes show a distinctive pattern of inheritance

in which the trait is passed from an affected female to all of her

children. Her daughters will likewise pass the trait on to all of

her children, but her sons do not transmit the trait at all.

The types of disorders which are inherited through

mutationsof the mitochondrial DNA tend to involve disorders

of nerve function, as neurons require large amounts of energy

to function properly. The best known of the mitochondrial dis-

orders is Leber hereditary optic neuropathy (LHON), which

involves bilateral central vision loss, which quickly worsens

as a result of the death of the optic nerves in early adulthood.

Other mitochondrial diseases include Kearns-Sayre syndrome,

myoclonus epilepsy with ragged red fibers (MERFF), and

mitochondrial encephalomyopathy, lactic acidosis and stroke-

like episodes (MELAS).

See alsoMitochondria and cellular energy; Mitochondrial

inheritance; Ribonucleic acid (RNA)

MMitochondrial InheritanceITOCHONDRIALINHERITANCE

Mitochondrial inheritance is the study of how mitochondrial

genes are inherited. Mitochondria are cellular organelles that

contain their own DNAand RNA, allowing them to grow and

replicate independent of the cell. Each cell has 10,000 mito-

chondria each containing two to ten copies of its genome.

Because mitochondria are organelles that contain their own

genome, they follow an inheritance pattern different from sim-

ple Mendelian inheritance, known as extranuclear or cytoplas-

mic inheritance. Although they posses their own genetic

material, mitochondria are semi-autonomous organelles

because the nuclear genome of cells still codes for some com-

ponents of mitochondria.

Mitochondria are double membrane-bound organelles

that function as the energy source of eukaryotic cells. Within

the inner membrane of mitochondria are folds called cristae

that enclose the matrix of the organelle. The DNA of mito-

chondria, located within the matrix, is organized into circular

duplex chromosomesthat lack histones and code for proteins,

rRNA, and tRNA. A nucleoid, rather than a nuclear envelope,

surrounds the genetic material of the organelle. Unlike the

DNA of nuclear genes, the genetic material of mitochondria

does not contain introns or repetitive sequences resulting in a

relatively simple structure. Because the chromosomes of mito-

chondria are similar to those of prokaryotic cells, scientists

hold that mitochondria evolved from free-living, aerobic bac-

teriamore than a billion years ago. It is hypothesized that mito-

chondria were engulfed by eukaryotic cells to establish a

symbiotic relationship providing metabolic advantages to each.

Mitochondria are able to divide independently without

the aid of the cell. The chromosomes of mitochondria are

replicated continuously by the enzyme DNA polymerase, with

each strand of DNA having different points of origin. Initially,

one of the parental strands of DNA is displaced while the other

parental strand is being replicated. When the copying of the

first strand of DNA is complete, the second strand is replicated

in the opposite direction. Mutation rates of mitochondria are

much greater than that of nuclear DNA allowing mitochondria

to evolve more rapidly than nuclear genes. The resulting phe-

womi_M 5/7/03 7:52 AM Page 393