The mitochondrial probe rhodamine 123 inhibits in isolated hepatocytes the degradation of short-lived proteins.
The fluorescent dye rhodamine 123 (R123) decreases the intracellular ATP levels and also inhibits the degradation of short-lived proteins in isolated hepatocytes. This inhibition affects lysosomal and, to some extent, non-lysosomal mechanisms. The degradation of short-lived proteins decreases more when ATP levels are less than 40% of those in control cells, in contrast to the reported linear correlation between ATP levels and degradation of long-lived proteins. R123 provides a powerful probe for clarifying the proteolytic mechanisms involved in degradation of short-lived proteins and the ATP requirements in protein degradation. Indeed, as illustrated, the results suggest different mechanisms for the degradation of short- and long-lived proteins. Moreover, they provide a warning for the clinical use of this reagent.
Vargas
J L
JL
Instituto de Investigaciones Citológicas de la Caja de Ahorros de Valencia, Centro asociado al Consejo Superior de Investigaciones Cientificas, Valencia, Spain.
Roche
E
E
Knecht
E
E
Aniento
F
F
Grisolía
S
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D005456:Fluorescent Dyes; D007700:Kinetics; D007976:Leupeptins / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D020112:Rhodamine 123; D012235:Rhodamines / Q000494:pharmacology*; D014966:Xanthenes / Q000494:pharmacology*
D005456:Fluorescent Dyes; D007976:Leupeptins; D011506:Proteins; D012235:Rhodamines; D014966:Xanthenes; D000643:Ammonium Chloride; D020112:Rhodamine 123; D000255:Adenosine Triphosphate