U n i t e d M i t o c h o n d r i a l D i s e a s e F o u n d a t i o n M itochondrial N ews M itochondrial N ews M itochondrial medicine has become one of the fastest
growing new disciplines in medicine (Luft 1994; 1995, Graff 1999). New mitochondrial diseases are being
described every year. Nearly one hundred different muta-
tions in mitochondrial DNA have been described, and
nearly 500 nuclear gene defects are associated with mito-
chondrial dysfunction. Not all of these genetic defects
cause measurable declines in oxidative phosphorylation -
the process by which food and oxygen are combined to
make energy (ATP). Nevertheless, even the mitochondri-
al diseases that do not cause measurable energy failures
can be catastrophic and difficult to diagnose. Our
expanding knowledge of the molecular, biochemical, and
clinical features of mitochondrial disorders has forced a
change in how scientists understand these complex dis-
eases. This article will review some of the hallmarks of
these disorders in adults, and outline some of the tests
that are required for diagnosis. Any disease. Any organ. Any age. This is perhaps the best general summary of the spectrum of mitochondr-
ial disease available (Christodoulou 1999). Mitochondrial diseases are notorious masqueraders (Kerr 1998). They
can cause symptoms that are indistinguishable from those
caused by common disorders. Only the behavior of the
mitochondrial disease over time sets it apart from its
more common cousins. Mitochondrial dysfunction has
now been linked to common maladies as diverse as infer-
tility (Jansen 1998), cancer (Susin 1998), migraine
headaches (Welch 1995), diabetes (Damore 1999), heart
disease (Hatch 1998, DiMauro 1998), blindness (Latkany
1999), deafness (Fischel 1999), kidney disease (Niaudet
1996), liver disease (Treem 1998), stroke (Heales 1999), the
toxicity of AIDS drugs (Barile 1998), Parkinson disease
(Kosel 1999), Alzheimer dementia (Fiskum 1999), and the
aging process itself (Wallace 1997). Epidemiologic studies
have established beyond doubt that when these chronic
disorders are studied as groups, they are complex and
have multiple causes - both genetic and environmental.
Mitochondrial disease does not cause a majority of any
one of the disorders listed. However, it is important to
remember that mitochondrial disease can be a cause of Adult Presentations of Mitochondrial Disease by Robert K. Naviaux, M.D., Ph.D. The Mitochondrial and Metabolic Disease Center, University of California, San Diego Continued on page 13 WHAT MITOCHONDRIA DO, AND WHAT CAN GO WRONG When the breakdown products of the food that we eat enter the mitochon- dria for processing, theyre passed along a well-orchestrated assembly line
made up of hundreds of proteins, each with a specific role to play in the energy
production process. Raw materials enter the beginning of the assembly line,
and ATP energy molecules come out the other side. The major steps in the energy extraction process are (see illustration): 1. Import and export of materials, such as fat and sugar derivatives, to and from the mitochondria 2. The breakdown of fatty acids through beta-oxidation and the removal of electrons in the citric acid cycle 3. The passage of electrons through the major complexes of the respiratory chain, or electron transport chain, and 4. The manufacture of ATP by ATP synthase. When any one of these steps is blocked, usually because a genetic defect has prevented the manufacture of a protein required for that step, mitochondrial MITOCHONDRIA INSIDE A CELL INSIDE THE MITOCHONDRION FAT & SUGAR "INTERMEDIATES" Mitochondrial DNA Beta Oxidation Citric Acid Cycle ATP ATP ATP (Energy) IV V III II I 3 4 2 1 Respirator y Chain ATP Synthesis Mitochondrial Myopathy: An Energy Crisis In The Cells by Sharon Hesterlee, Quest, Volume 6, Number 4, August 1999 (Excerpts) Reprinted by permission of the Muscular Dystrophy Association This is the first of a two-part Quest series [Excerpts] about mitochondrial myopathy. This article covers the basic biology of mitochondria and explains inheritance patterns and determinants of severity in mitochondrial diseases. Part 2 will discuss diagnosis and treatment, including a look at new information about mitochondrial diseases in the research pipeline. Continued on page 5 2 Spring 2000 Volume 5 Issue 1 Mitochondrial News United Mitochondrial Disease Foundation P.O. Box 1151 Monroeville, PA 15146-1151 Phone 412-793-8077 Fax 412-793-6477 email: umdf@nb.net http://www.umdf.org Board of Trustees Chuck Mohan, Chairman Marsha Barnett Bruce H. Cohen, M.D. John DiCecco Mark Fleming Jane Clarke McManus Lee Neff Nick Rillo Scientific Advisors Gerard T. Berry, M.D. Richard G. Boles, M.D. Salvatore DiMauro, M.D. Carol Greene, M.D. Richard Haas, M.B., B. Chir. Charles L. Hoppel, M.D. Richard Kelley, M.D., Ph.D. Douglas S. Kerr, M.D., Ph.D. Nicholas Krawiecki, M.D. Arnold Munnich, M.D., Ph.D. Robert K. Naviaux, M.D., Ph.D. William L. Nyhan, M.D., Ph.D. Brian H. Robinson, Ph.D. John Shoffner, M.D. Eric Shoubridge, Ph.D. D. M. Turnbull, M.D., Ph.D. Rajiv R. Varma, M.D. Georgirene Vladutiu, Ph.D. Douglas C. Wallace, Ph.D. National Office Leslie Boyer, Executive Director Antoinette R. Beasley Robert Bolewitz Sheryl Cohen Julie Hughes Kara Strittmatter The opinions reported in the newsletter are not necessarily endorsed by the United Mitochondrial Disease Foundation. Our intent is to keep you informed, and we ask that you always discuss any diagnoses, treatments or medications with your personal physician.