Mitochondrial DNA from platelets of sporadic ALS patients restores normal respiratory functions in rho(0) cells.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, which affects the anterior horn cells of the spinal cord and cortical motor neurons. A pathophysiological role for mtDNA mutations was postulated based on the finding that cybrids obtained from mitochondria of sporadic ALS patients exhibited impaired respiratory chain activities, increased free radical scavenging enzymes, and altered calcium homeostasis. To date, however, no distinct mtDNA alterations associated with ALS have been reported. Therefore, we reexamined the hypotheses that mtDNA mutations accumulate in ALS and that cybrids generated from ALS patients' blood have impaired mitochondrial respiration. Cybrid cell lines were generated from 143B osteosarcoma rho(0) cells and platelet mitochondria of sporadic ALS patients or age-matched controls. We found no statistically significant differences in mitochondrial respiration between ALS and control cybrids, even when the electron transport chain was stressed with low concentrations of respiratory chain inhibitors. Mitochondrial respiratory chain enzyme activities were also normal in ALS cybrids, and there was no increase in free radical production. Therefore, we showed that mtDNA from platelets of ALS patients was able to restore normal respiratory function in rho(0) cells, suggesting that the presence of mtDNA mutations capable of affecting mitochondrial respiration was unlikely.