Early problems in mitochondrial cleanup and energy use may drive organ damage progression in Fabry heart disease

Mitochondrial dysfunction is identified as a key driver of cardiomyopathy in Fabry disease, with age-related progression leading to severe cardiac abnormalities.

• Impaired energy metabolism is associated with organ damage in Fabry disease, particularly affecting the heart.
• A humanized mouse model of Fabry disease exhibited defects in mitophagy and mitochondrial respiration.
• Increased reactive oxygen species were observed, contributing to lysosomal dysfunction and a cycle of damage.
• Defects in mitochondrial function worsened with age, leading to cardiac hypertrophy and diastolic dysfunction.
• L-arginine treatment promoted mitochondrial rescue and prevented the development of cardiac abnormalities.

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