CISD3/MiNT is required for complex I function, mitochondrial integrity, and skeletal muscle maintenance.

Area of Science:

• Mitochondrial biology
• Muscle physiology
• Protein biochemistry

Background:

• Mitochondria are vital for muscle metabolism and function.
• CDGSH Iron Sulfur Domain-containing (CISD/NEET) proteins support mitochondrial health.
• Aging reduces CISD protein levels, contributing to muscle degeneration.

Purpose of the Study:

• To investigate the role of the inner mitochondrial CISD protein, CISD3/MiNT, in skeletal muscle.
• To understand CISD3's function and its impact on muscle structure and mitochondria.

Main Methods:

• Studied CISD3-deficient mice to observe muscle atrophy.
• Analyzed skeletal muscle and mitochondrial function and structure.
• Utilized coevolutionary and structural computational tools to model protein interactions.

Main Results:

• CISD3 deficiency led to muscle atrophy with proteomic similarities to Duchenne muscular dystrophy.
• Impaired skeletal muscle and mitochondrial function and structure were observed.
• CISD3 interacts with and donates [2Fe-2S] clusters to NDUFV2, a subunit of Complex I.

Conclusions:

• CISD3/MiNT is essential for the biogenesis and function of mitochondrial Complex I.
• This finding highlights CISD3's critical role in maintaining muscle function.
• Targeting CISD3 may offer therapeutic strategies for muscle degeneration syndromes and aging.