Complex I function and supercomplex formation are preserved in liver mitochondria despite progressive complex III...

Area of Science:

• Mitochondrial biology
• Cellular respiration
• Biochemistry

Background:

• Functional oxidative phosphorylation depends on assembled mitochondrial respiratory complexes and supercomplexes.
• BCS1L is essential for incorporating the Rieske iron-sulfur protein into complex III, a key step in its assembly.
• Previous studies suggested this subunit is vital for supercomplex formation and complex I stability.

Purpose of the Study:

• To investigate the role of fully assembled complex III in supercomplex formation within intact liver tissue.
• To assess the impact of BCS1L deficiency on mitochondrial function and supercomplexes in a transgenic mouse model.

Main Methods:

• Utilized a transgenic mouse model with a Bcs1l mutation causing decreased BCS1L expression and Rieske protein levels.
• Employed blue native gel electrophoresis to analyze supercomplex formation at various ages.
• Assessed mitochondrial complex activity using high-resolution respirometry.

Main Results:

• In young mutant mice, supercomplexes were similar to wild type.
• In older mutant mice with liver disorder, complex III was predominantly a pre-complex lacking the Rieske subunit.
• Despite complex III deficiency, main supercomplexes were detected, containing the pre-complex form.
• Complex I function was preserved and even upregulated, with increased free complex abundance.

Conclusions:

• A complex III pre-complex lacking the Rieske subunit can participate in supercomplex formation.
• Deficient complex III assembly does not necessarily impair complex I function or overall respiratory chain stability.
• The study highlights the adaptability of mitochondrial respiratory chain assembly under specific deficiency conditions.