Mitochondrial respirasome-like supercomplexes support metabolic flexibility in yeast

Area of Science:

• Biochemistry
• Molecular Biology
• Cellular Respiration

Background:

• Mitochondrial respiratory chain (MRC) complexes form supercomplexes (SCs) vital for energy production.
• Understanding SC physiological roles is key to mitochondrial function but limited by experimental models.
• Yeast SCs (III₂IV₁ and III₂IV₂) enhance respiration by aiding cytochrome c diffusion.

Purpose of the Study:

• Investigate the physiological relevance of distinct SC conformations and MRC plasticity.
• Elucidate the specific roles of SCs in yeast mitochondrial bioenergetics.
• Determine how SC structure impacts substrate-specific respiration.

Main Methods:

• Engineered a yeast strain expressing a covalently-linked III₂IV₂ SC, mimicking wild-type structure.
• Assessed respiratory activity in the engineered yeast strain.
• Analyzed the impact of the tethered SC on cytosolic NADH-driven respiration and interactions with Nde1.

Main Results:

• The tethered III₂IV₂ SC supported robust respiratory activity.
• Selective impact on cytosolic NADH-driven respiration was observed.
• Distinct interactions with NADH dehydrogenase Nde1 were identified, influencing respiration.

Conclusions:

• Substrate-specific, respirasome-like SCs in yeast mitochondria optimize electron flux.
• Engineered SCs provide insights into MRC plasticity and metabolic flexibility.
• The study highlights the functional significance of SC conformation in bioenergetics.