From Alzheimer’s to Zebrafish: Eclectic Science and Regulatory Stories 114
There would appear to be neither any link nor any obvious similarities among Parkinson’s
disease, exercise intolerance, diabetes and organ failure in sepsis, except that each is a
health problem. Anything else common to this disparate group would have to be quite
fundamental. Such is the case: we now know that the common link is the mitochrondrion,
which has been deemed the mighty dynamo of the cell.1 Each of the conditions listed
results from a pathology that inhibits mitochondrial activity and results in failure to pro-
vide the necessary energy for normal metabolic processes.
Mitochondria, at least until recently, have been a badly kept secret.2 (The word itself
is derived from the Greek mitos, meaning thread, and chrondrin, meaning small grain.)
One reason for the secrecy is that bioenergetics—the study of energy production in the
mitochondria—is considered to be a difficult and obscure field. Second, molecular biolo-
gists did not recognize the far-reaching implications and applications of the discovery
of mitochondrial genes. For these reasons, it is not surprising that many of us may not
know that mitochondria are the power generators residing inside our living cells and that
by using oxygen to burn food, they produce all the energy we need to live and support
growth. There are usually hundreds or thousands of them in a single cell. One billion of
them would fit comfortably in a grain of sand. Mitochondria are present in every cell of
the body except red blood cells.3
How important are mitochondria? They are now seen as the key ingredient that made
complex life possible.4 Nevertheless, despite their ubiquitous nature and criticality, mito-
chondria are at best a mystery. This article briefly describes their history, derivation and
function, and the variety of mitochondrial diseases and treatments. The references cited
are excellent resources for further information.
History
The first scientists to recognize the existence of mitochondria were working during the
mid-1800s. In 1857, Albert von Kolliker described what he called “granules” in the cells of
muscles.5 The true discovery, however, may have occurred in 1886, when Richard Altman,
a cytologist, identified organelles using a dye technique. (Organelles are tiny organs
within cells that are dedicated to specific tasks.) He called them “bioblasts.” Carl Benda, in
1898, coined the term “mitochondria.” Many more individuals began to work on mito-
chondria over the next few decades, each of whom discovered an important function they
perform within the cell. In 1912, Otto Heinrich Warburg, a German biochemist, hypoth-
esized that an enzyme within cells enabled oxygen to be processed. Further research was
conducted by David Keilin in 1923 to show how the oxidation state of cytochromes was
changed during respiration. (Cytochromes are hemoproteins responsible for electron
transport.) Adenosine triphosphate (ATP), the transporter of chemical energy within cells,
was isolated in 1929 by C.H. Fiske and Y. Subbarow. Then, independent studies by H.M.
Kalckar and V.A. Belitser showed how the addition of a phosphate to protein aids in cel-
lular respiration, a process called oxidative phosphorylation (OXPHOS).6
In 1950, Eugene Kennedy and Albert Lehninger ascertained the means by which oxi-
dation occurs within mitochondria. It was not until 1978 that Peter Mitchell described the
diffusion of hydrogen ions across membranes and its relationship to ATP during respira-
tion in eukaryotic cells. This helped establish the overall purpose of mitochondria. More
recently, Paul Boyer discovered mitochondria’s role in ATP synthase (or the combining
of adenosine diphosphate and inorganic phosphate to create ATP). He was awarded the
Nobel Prize in Chemistry in 1997 for his seminal work.7
Mitochondrial diseases were not reported until 1962, when Rolf Luft described
the first case, a young Swedish woman suffering from non-thyroidal hypermetabolism
due to loose coupling of muscle mitochondria.8 Later, the sequencing of the mitochron-
drial genome and the recognition in the 1980s that defects of this genome cause disease
sparked new interest in these disorders. They include among others, diabetes and its
There would appear to be neither any link nor any obvious similarities among Parkinson’s
disease, exercise intolerance, diabetes and organ failure in sepsis, except that each is a
health problem. Anything else common to this disparate group would have to be quite
fundamental. Such is the case: we now know that the common link is the mitochrondrion,
which has been deemed the mighty dynamo of the cell.1 Each of the conditions listed
results from a pathology that inhibits mitochondrial activity and results in failure to pro-
vide the necessary energy for normal metabolic processes.
Mitochondria, at least until recently, have been a badly kept secret.2 (The word itself
is derived from the Greek mitos, meaning thread, and chrondrin, meaning small grain.)
One reason for the secrecy is that bioenergetics—the study of energy production in the
mitochondria—is considered to be a difficult and obscure field. Second, molecular biolo-
gists did not recognize the far-reaching implications and applications of the discovery
of mitochondrial genes. For these reasons, it is not surprising that many of us may not
know that mitochondria are the power generators residing inside our living cells and that
by using oxygen to burn food, they produce all the energy we need to live and support
growth. There are usually hundreds or thousands of them in a single cell. One billion of
them would fit comfortably in a grain of sand. Mitochondria are present in every cell of
the body except red blood cells.3
How important are mitochondria? They are now seen as the key ingredient that made
complex life possible.4 Nevertheless, despite their ubiquitous nature and criticality, mito-
chondria are at best a mystery. This article briefly describes their history, derivation and
function, and the variety of mitochondrial diseases and treatments. The references cited
are excellent resources for further information.
History
The first scientists to recognize the existence of mitochondria were working during the
mid-1800s. In 1857, Albert von Kolliker described what he called “granules” in the cells of
muscles.5 The true discovery, however, may have occurred in 1886, when Richard Altman,
a cytologist, identified organelles using a dye technique. (Organelles are tiny organs
within cells that are dedicated to specific tasks.) He called them “bioblasts.” Carl Benda, in
1898, coined the term “mitochondria.” Many more individuals began to work on mito-
chondria over the next few decades, each of whom discovered an important function they
perform within the cell. In 1912, Otto Heinrich Warburg, a German biochemist, hypoth-
esized that an enzyme within cells enabled oxygen to be processed. Further research was
conducted by David Keilin in 1923 to show how the oxidation state of cytochromes was
changed during respiration. (Cytochromes are hemoproteins responsible for electron
transport.) Adenosine triphosphate (ATP), the transporter of chemical energy within cells,
was isolated in 1929 by C.H. Fiske and Y. Subbarow. Then, independent studies by H.M.
Kalckar and V.A. Belitser showed how the addition of a phosphate to protein aids in cel-
lular respiration, a process called oxidative phosphorylation (OXPHOS).6
In 1950, Eugene Kennedy and Albert Lehninger ascertained the means by which oxi-
dation occurs within mitochondria. It was not until 1978 that Peter Mitchell described the
diffusion of hydrogen ions across membranes and its relationship to ATP during respira-
tion in eukaryotic cells. This helped establish the overall purpose of mitochondria. More
recently, Paul Boyer discovered mitochondria’s role in ATP synthase (or the combining
of adenosine diphosphate and inorganic phosphate to create ATP). He was awarded the
Nobel Prize in Chemistry in 1997 for his seminal work.7
Mitochondrial diseases were not reported until 1962, when Rolf Luft described
the first case, a young Swedish woman suffering from non-thyroidal hypermetabolism
due to loose coupling of muscle mitochondria.8 Later, the sequencing of the mitochron-
drial genome and the recognition in the 1980s that defects of this genome cause disease
sparked new interest in these disorders. They include among others, diabetes and its