Phosphatidylethanolamine made in the inner mitochondrial membrane is essential for yeast cytochrome bc₁ complex...

Area of Science:

• Mitochondrial biology
• Lipid metabolism
• Cellular respiration

Background:

• Phosphatidylethanolamine (PE) is vital for mitochondrial inner membrane (IM) function.
• One eukaryotic PE biosynthetic pathway occurs in the IM, catalyzed by phosphatidylserine decarboxylase (Psd1).
• Psd1 deletion is lethal and impairs mitochondrial function, suggesting inefficient non-mitochondrial PE import into the IM.

Purpose of the Study:

• To investigate the role of IM-synthesized PE in mitochondrial function.
• To challenge the dogma of PE trafficking by examining PE movement across the intermembrane space (IMS).
• To determine if PE synthesized by Psd1 in the IM is essential for cytochrome bc1 complex (III) activity.

Main Methods:

• Re-wiring yeast PE metabolism by relocating Psd1 to the outer mitochondrial membrane or endomembrane system.
• Assessing PE transport across the IMS in both directions.
• Analyzing cytochrome bc1 complex (III) function in yeast strains with altered Psd1 localization or mutations in the Qcr7 subunit.

Main Results:

• PE can be transported across the IMS in both directions.
• PE synthesis within the IM is critical for cytochrome bc1 complex (III) function.
• Mutations in the conserved PE-binding site of Qcr7 impair complex III activity, mimicking PSD1 deletion.

Conclusions:

• The study challenges current models of PE trafficking.
• Psd1-synthesized PE in the IM directly supports the intrinsic functionality of cytochrome bc1 complex (III).
• Mitochondrial PE synthesis is essential for cellular respiration and viability.