here is some general info
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Ann Clin Lab Sci 2001 Jan;31(1):25-67
Mitochondrial medicine--molecular pathology of defective oxidative
phosphorylation.
Fosslien E.
Department of Pathology, College of Medicine, University of Illinois at Chicago,
60612, USA. [log in to unmask]
Different tissues display distinct sensitivities to defective mitochondrial
oxidative phosphorylation (OXPHOS). Tissues highly dependent on oxygen such as
the cardiac muscle, skeletal and smooth muscle, the central and peripheral
nervous system, the kidney, and the insulin-producing pancreatic beta-cell are
especially susceptible to defective OXPHOS. There is evidence that defective
OXPHOS plays an important role in atherogenesis, in the pathogenesis of
Alzheimer's disease, Parkinson's disease, diabetes, and aging. Defective OXPHOS
may be caused by abnormal mitochondrial biosynthesis due to inherited or
acquired mutations in the nuclear (n) or mitochondrial (mt) deoxyribonucleic
acid (DNA). For instance, the presence of a mutation of the mtDNA in the
pancreatic beta-cell impairs adenosine triphosphate (ATP) generation and insulin
synthesis. The nuclear genome controls mitochondrial biosynthesis, but
mtDNA has
a much higher mutation rate than nDNA because it lacks histones and is exposed
to the radical oxygen species (ROS) generated by the electron transport chain,
and the mtDNA repair system is limited. Defective OXPHOS may be caused by
insufficient fuel supply, by defective electron transport chain enzymes
(Complexes I - IV), lack of the electron carrier coenzyme Q10, lack of oxygen
due to ischemia or anemia, or excessive membrane leakage, resulting in
insufficient mitochondrial inner membrane potential for ATP synthesis by the
F0F1-ATPase. Human tissues can counteract OXPHOS defects by stimulating
mitochondrial biosynthesis; however, above a certain threshold the lack of ATP
causes cell death. Many agents affect OXPHOS. Several nonsteroidal
anti-inflammatory drugs (NSAIDs) inhibit or uncouple OXPHOS and induce the
'topical' phase of gastrointestinal ulcer formation. Uncoupled mitochondria
reduce cell viability. The Helicobacter pylori induces uncoupling. The
uncoupling that opens the membrane pores can activate apoptosis. Cholic
acid in
experimental atherogenic diets inhibits Complex IV, cocaine inhibits
Complex I,
the poliovirus inhibits Complex II, ceramide inhibits Complex III, azide,
cyanide, chloroform, and methamphetamine inhibit Complex IV. Ethanol abuse and
antiviral nucleoside analogue therapy inhibit mtDNA replication. By contrast,
melatonin stimulates Complexes I and IV and Gingko biloba stimulates
Complexes I
and III. Oral Q10 supplementation is effective in treating cardiomyopathies and
in restoring plasma levels reduced by the statin type of cholesterol-lowering
drugs.
PMID: 11314862 [PubMed - in process]
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Ray Strand
Prairie Sky Design
-----------------( on the Edge of the Prairie Abyss )---------------
when the sky is clear
the ground is visible
49/dx PD 2 yrs/40? onset/retired
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