Ablation of

Area of Science:

• Mitochondrial biology
• Cellular metabolism
• Skeletal muscle physiology

Background:

• The Sorting and Assembly Machinery (SAM) complex, particularly the Sam50 subunit, is essential for β-barrel protein assembly in mitochondrial membranes.
• Sam50 stabilizes the mitochondrial intermembrane space bridging (MIB) complex, vital for protein transport and mitochondrial structure.
• The precise role of Sam50 in skeletal muscle mitochondrial structure and metabolism is not well understood.

Approach:

• Utilized serial block-face-scanning electron microscopy (SBF-SEM) and 3D rendering to analyze mitochondrial morphology in Sam50-deficient and wild-type (WT) myotubes.
• Assessed autophagosome structure in human myotubes.
• Employed Gas Chromatography-Mass Spectrometry (GC-MS) based metabolomics to profile metabolic changes.
• Measured oxidative capacity using the XF24 Seahorse Analyzer.

Key Points:

• Sam50 deficiency led to increased mitochondrial fragmentation and autophagosome formation in myotubes.
• Metabolomic analysis revealed altered metabolism of propanoate, amino acids (ß-Alanine, phenylalanine, tyrosine), and fatty acids.
• Ablation of Sam50 impaired mitochondrial oxidative capacity in both murine and human myotubes.

Conclusions:

• Sam50 plays a critical role in maintaining mitochondrial integrity, cristae structure, and metabolic function in skeletal muscle.
• Understanding Sam50's function provides insights into mitochondrial disorders and skeletal muscle health.
• This study highlights Sam50 as a key regulator of mitochondrial homeostasis and energy metabolism.