Stress-induced mitochondrial depolarization and oxidative damage in PSP cybrids.
Increased oxidative damage and mitochondrial dysfunction have been suggested to play critical roles in the pathogenesis of progressive supranuclear palsy (PSP) yet the specific intracellular defects which cause and can result from these oxidative and bioenergetic defects remain unclear. To extend our previous PSP cybrid findings, we measured electron transport chain (ETC) activities in cell lines expressing mitochondrial genes from patients with PSP. Further, we measured changes in mitochondrial membrane potential as well as lipid peroxidation in PSP and control cybrids in response to mitochondrial toxins. We observed significant decreases in complex I+III activity in PSP cybrids as well as significant increases in markers of lipid oxidative damage as compared to control cybrids. These results coupled with previous reports from this and other laboratories strongly suggest contributory roles of mitochondrial dysfunction and oxidative damage in PSP, possibly due to genetic abnormalities and/or damage of mitochondrial DNA.
Chirichigno
Jason W
JW
Department of Neurology and Neuroscience, Room A-503, Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA.
Manfredi
Giovanni
G
Beal
M Flint
MF
Albers
David S
DS
D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics*; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000235:genetics*; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D013494:Supranuclear Palsy, Progressive / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D014118:Toxins, Biological
D004272:DNA, Mitochondrial; D014118:Toxins, Biological