Involvement of mitochondria in cell degeneration.

Human WI-38 fibroblasts were microinjected with isolated mitochondria, and survival of the injected cells was followed. More than 95% of the cells were alive and able to divide when they were injected with fresh mitochondrial preparations having a high respiratory control ratio (RCR). The presence of lysosomes was found to be toxic to the cells, and hence mitochondria had to be isolated without being contaminated by lysosomes. The microinjection of isolated mitochondria from old rats induced a 20% degeneration of the injected cells. The proportion of dead cells was also found to be dependent on the metabolic control of the injected mitochondria. Moreover, an easily metabolized energy substrate such as D(-)-beta-hydroxybutyrate sodium salt was able to inhibit, in a dose-dependent manner, cell degeneration induced by microinjection of uncoupled mitochondria. These results suggest that modifications of mitochondria leading to their uncoupling are harmful to the cells, and this can explain some of the degenerative processes observed in natural or externally induced cell death.