Diseases

Overview

History of Mitochondria in Science and Medicine

Verne Mendel was formed to capitalize on discoveries of mitochondrial DNA damage prevention and protection of mitochondrial function. Mitochondria are powerhouses in cells and were originally derived from bacteria, which became incorporated into cells for the purpose of producing energy more efficiently. Verne Mendel is the only company founded specifically to develop treatments of mitochondrial diseases based on compounds which are active in gold standard models of metabolic and Neurodegeneration, in which toxin based models mitochondrial DNA damage occurs.

Carl Benda proposed the name mitochondria in 1898 and the name has its origin in the Greek language where mitos means thread and chondros means granule. In the early twentieth century mitochondria were recognized as having metabolic roles.

Mitochondria produce energy from food and store it in a compound called ATP (adenosine triphosphate). In addition to supplying cellular energy, these organelles are also involved in several other cell functions including cell signaling, cellular differentiation, and cell growth and cell death. Thus, mitochondria play an important role in many cellular functions in heath and disease.

In 1962 Lars Ernster and Rolf Luft described the first case of a patient having a mitochondrial disease in which she suffered from extreme hypermetabolism of non-thyroid origin and she had gigantic mitochondria in muscle.

In 1962 G. Milton Shy described mitochondrial proliferation, referred to as called ragged red fibers in patients with mypopathy.

In 1962 W. King Engel used modified Gomori trichrome histochemical stain to stain skeletal muscle of some patients with mitochondrial disease and referred to them as ragged red fibers.

Mitochondrial DNA (mtDNA) was first discovered in 1963 by Margit M. K. Nass and Sylvan Nass by electron microscopy, and by Ellen Haslbrunner, Hans Tuppy and Gottfried Schatz by biochemical assays on highly purified mitochondrial fractions.

In 1970 Lynn Margulies, based on her studies during the 1960s proposed that mitochondria were bacteria co-opted into mammalian cells for the purpose of producing energy more efficiently.

In 1975 M. Koenigsberger describes a case of MELAS - mitochondrial myopathy, encephalopathy, and lactic acidosis, stroke-like episodes

In 1990, Y. Goto reported the first mitochondrial point mutation (from the base pair adenine to guanine) associated with MELAS syndrome at base pair 3243 (A3243G). Since then, many additional point mutations have been reported.

In 1981 the human mitochondrial genome sequence was mapped by S. Anderson, a mere 16,569 base pairs. Subsequent sequencing of other individual's mitochondrial genomes revealed substantial differences to the Cambridge Reference Sequence. itochondrial DNA contains 37 genes, all of which are essential for normal mitochondrial function. Thirteen of these genes provide instructions for making enzymes involved in oxidative phosphorylation, a means to produce energy. This led to the development of mitochondrial DNA sequencing for diagnostic purposes and subsequently for genealogical and forensic applications.

In 1988, the first disorder associated with a mitochondrial DNA deletion, chronic progressive external ophthalmoplegia was reported and subsequently Leber hereditary optic neuropathy was reported. Thereafter other major forms of mitochondrial diseases that more typically present in childhood were recognized, including myoclonic epilepsy with ragged-red fibers and mitochondrial encephalopathy with lactic acidosis and stroke.

It was also recognized that nuclear encoded defects affect mitochondrial function and that mitochondrial disorders contributed to the pathogenesis of many clinical and metabolic diseases and that mitochondria play a role in apoptosis, cell injury, and cell death. In 1991 biochemical and molecular analysis of mitochondrial DNA defects became commercially available. Environmental toxins and AIDS drugs such as AZT (azidothymidine), didanosine and zalcitabine are known to deplete mitochondrial DNA by inhibiting its replicating machinery.

Forensic and molecular anthropology has become a productive field of intellectual inquiry. Since mitochondrial DNA is only transmitted maternally, it is often used to trace or identify an individual's maternal lineage. In 1987 Allan Wilson published mapping data indicating the origins of man from an African Eve who lived some 200,000 years ago.

The data suggests expansion of the human race to other areas from very small numbers in a period starting perhaps 70,000 years ago. The early history of the human migration into Europe began about 45,000 years ago.

Doug Wallace has demonstrated the lineage of Native Americans from Polynesian ancestors who migrated from Siberia across the Bering peninsula about 13,00 years ago into the Americas.

The average number of base pair differences between two human mitochondrial genomes is 38.5 among non-Africans, 76.6 among Africans and 61.6 among all humans. Mitochondrial DNA variation correlates with the ethnic and geographical origin of the individual much more than nuclear DNA.