Mitochondrial DNA and respiratory chain function in spinal cords of ALS patients

TLDR

Amyotrophic lateral sclerosis is a neurodegenerative disease characterized by selective motor neuron death. The study aimed to investigate whether mitochondrial DNA alterations and respiratory chain dysfunction contribute to ALS pathogenesis. Researchers examined mitochondrial DNA integrity and respiratory chain enzyme activities in postmortem spinal cord tissues from ALS patients and neurologically normal controls. ALS spinal cords exhibited elevated mutant mtDNA, reduced total mtDNA, and diminished citrate synthase and respiratory chain complex activities, indicating mitochondrial loss.

Abstract

Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective motor neuron death. In order to address the question of a putative role of mitochondrial dysfunction in the pathogenesis of ALS, we studied the mitochondrial DNA (mtDNA) and mitochondrial respiratory chain enzyme activities in spinal cords of ALS patients and in control subjects without neuropathologic abnormalities. Using a ‘double PCR and digestion’ technique to estimate the levels of randomly distributed point mutations in two small regions of the mtDNA, we found significantly higher levels of mutant mtDNA in the spinal cord of ALS patients compared to controls. No large‐scale rearrangements were found, but the amount of mtDNA, measured by Southern blot, was significantly lower in the ALS samples. This reduction correlated well with a decrease of citrate synthase (CS) activity, a mitochondrial marker, as were the activities of respiratory chain complexes I + III, II + III, and IV, suggesting a loss of mitochondria in ALS spinal cords.