Mitochondrial dysfunction in blood cells from amyotrophic lateral sclerosis patients

Area of Science:

• Biochemistry
• Neuroscience
• Genetics

Background:

• Mitochondrial dysfunction is a known factor in amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by motor neuron degeneration.
• Previous studies indicate abnormalities in both central nervous system and muscle mitochondria in ALS patients, suggesting a systemic disease process.

Purpose of the Study:

• To investigate mitochondrial function in blood cells of amyotrophic lateral sclerosis (ALS) patients compared to healthy controls.
• To explore the potential of blood cell mitochondrial function as a biomarker for ALS.

Main Methods:

• A case-control study involving 24 ALS patients and 21 age-matched controls.
• Isolation of platelets and peripheral blood mononuclear cells for measurement of mitochondrial oxygen consumption.
• Normalization of respiratory values to cell count, citrate synthase activity, and mitochondrial DNA copy number.

Main Results:

• Complex IV (cytochrome c-oxidase) activity, normalized to mitochondrial content, was decreased in platelets and mononuclear cells of ALS patients.
• Mitochondrial content was found to be increased in platelets of ALS patients.
• In mononuclear cells, complex I activity declined, and mitochondrial content increased with advancing disease stage.

Conclusions:

• Reduced complex IV activity in blood cells, when normalized to mitochondrial content, supports systemic mitochondrial involvement in amyotrophic lateral sclerosis (ALS).
• An apparent compensatory increase in cellular mitochondrial content was observed in ALS patients.
• Mitochondrial function in blood cells warrants further investigation as a potential biomarker for ALS.