CTRP1 regulates skeletal muscle differentiation through quality control of mitochondrial dynamics and function

Area of Science:

• Mitochondrial biology
• Muscle physiology
• Cellular differentiation

Background:

• Mitochondrial dysfunction is a key feature of myopathies, affecting skeletal muscle differentiation and function.
• The role of specific proteins in regulating mitochondrial dynamics and muscle development is an area of active research.

Purpose of the Study:

• To investigate the role of C1q/TNF-related protein 1 (CTRP1) in mitochondrial dynamics and skeletal muscle differentiation.
• To determine if CTRP1 deficiency contributes to myopathic conditions.

Main Methods:

• Utilized myoblast cell cultures and skeletal muscle-specific knockout (CTRP1 KO^ΔACTA) mouse models.
• Assessed mitochondrial morphology, function (membrane potential, respiration), and myogenic differentiation capacity.
• Analyzed dynamin-related protein 1 (DRP1) recruitment and CTRP1 expression in patient muscle biopsies.

Main Results:

• Loss of CTRP1 impaired myotube formation, reduced muscle fiber size and strength, and shifted fiber type composition.
• CTRP1 deficiency caused mitochondrial disorganization, reduced cristae density, diminished membrane potential, and impaired oxidative respiration.
• Defective DRP1 recruitment was observed in CTRP1-deficient cells; restoring CTRP1 or mitochondrial transplantation rescued function.
• CTRP1 levels decreased with disease severity in human myopathy patient samples.

Conclusions:

• CTRP1 is essential for maintaining mitochondrial quality and supporting myogenic differentiation.
• CTRP1 plays a critical role in skeletal muscle health and function.
• CTRP1 represents a potential therapeutic target for mitochondrial myopathies.