Figure 5.

Current pathological hypotheses and therapeutic targets. The currently known cascade of main events leading to myofiber degeneration in ColVI-deficient skeletal muscle is shown. Mitochondrial dysfunction (due in part to the defective permeability transition pore (PTP) opening) triggers an energetic imbalance with the increased levels of phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), Ca²⁺ overload and the production of reactive oxygen species (ROS). Lack of autophagy induction exacerbates the cellular dysfunction because defective mitochondria and proteins (such as p62 aggregates) are not cleared from the cytoplasm. Together, these defects lead to increased apoptosis. Potential therapeutic interventions are indicated in green.