Prenatal and progressive coenzyme Q₁₀ administration to mitigate muscle dysfunction in mitochondrial disease

Area of Science:

• Mitochondrial Biology
• Developmental Biology
• Genetics

Background:

• ADCK genes encode mitochondrial kinases crucial for Coenzyme Q (CoQ) biosynthesis.
• ADCK2 haploinsufficiency in humans causes adult-onset mitochondrial myopathy with reduced CoQ levels.
• Current CoQ10 treatments offer only partial recovery, highlighting the need for early intervention.

Purpose of the Study:

• To investigate the role of Adck2 in muscle development, function, and regeneration throughout life.
• To examine the impact of Adck2 deficiency on skeletal muscle from embryonic stages to aging.
• To assess the therapeutic potential of Coenzyme Q10 (CoQ10) supplementation during development.

Main Methods:

• Utilized Adck2 heterozygous mice for developmental and aging studies.
• Employed immunohistochemistry, CoQ level analysis, and mitochondrial respiration assays.
• Conducted muscle transcriptome analysis and functional performance tests.

Main Results:

• Adck2 heterozygous embryos showed developmental delays and skeletal muscle defects, with prenatal CoQ10 mitigating these issues.
• Heterozygous mice exhibited impaired myogenic differentiation and accelerated age-related muscle wasting.
• Progressive CoQ10 administration protected mitochondrial function and skeletal muscle integrity.

Conclusions:

• Revealed novel embryonic defects in mammals associated with CoQ deficiencies due to ADCK2 mutations.
• Characterized the progressive nature of the Adck2 mouse phenotype from development through aging.
• Demonstrated the protective efficacy of developmental CoQ10 supplementation against Adck2-related defects.