How do mitochondrial disorders reduce the energy available to muscles?

Mitochondrial disorders reduce the energy available to muscles primarily by impairing the function of the electron transport chain (ETC). The ETC is the primary apparatus within mitochondria responsible for generating adenosine triphosphate (ATP), which serves as the essential fuel for muscle contraction.123

When mutations in either nuclear or mitochondrial DNA cause deficiencies in the proteins that constitute the ETC, the cell's ability to produce ATP is compromised. This dysfunction leads to several negative consequences for muscle tissue:412

• Reduced ATP Production: The primary energy-generating process is hindered, leaving muscles with insufficient fuel for normal activity.12
• Metabolic Shift: Because oxidative metabolism is impaired, muscles may attempt to compensate by relying on the nonoxidative breakdown of stored glycogen. This process is less efficient and often results in the excessive production of lactic acid.5
• Cellular Damage: Dysfunctional mitochondria may produce toxic reactive oxygen species, which cause oxidative stress and can lead to cell death. Additionally, damaged mitochondria may release factors that trigger apoptosis, or programmed cell death.412