Identification of drug candidates which increase cytochrome c oxidase activity in deficient patient fibroblasts.
Cytochrome c oxidase (COX) activity reflects the expressed level of respiratory chain complexes, mtDNA levels, titer and mass of mitochondria. Activity is also indicative of the overall fitness of mt-transcription factors and the import, transcription and translation of mt-proteins. We have developed a high-throughput assay to measure COX activity using live cells to screen chemical libraries for compounds capable of increasing COX activity. These libraries have revealed four examples which elevated the activities of COX in NIH-3T3 fibroblasts and in fibroblasts from patients with COX defects independent of the peroxisome proliferator activated receptor family.
Metabolism Research Programme, Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
Mary
M
Maj
Niroshan
N
Sriskandarajah
Vinci
V
Hung
Ikennah
I
Browne
Bhavank
B
Shah
Anita
A
Weadge
Nicola L
NL
Jamieson
Michael
M
Tropak
Jessie M
JM
Cameron
Jane B
JB
Addis
Brian H
BH
Robinson
D000818:Animals; D015153:Blotting, Western; D002461:Cell Line, Transformed; D004396:Coloring Agents; D003576:Electron Transport Complex IV / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells
D004396:Coloring Agents; D003576:Electron Transport Complex IV