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.