Specific requirements of nonbilayer phospholipids in mitochondrial respiratory chain function and formation

Autor: Vishal M. Gohil, Writoban Basu Ball, Erin N. Pryce, Charli D. Baker
Rok vydání: 2016
Předmět:
Zdroj: Molecular Biology of the Cell
ISSN: 1939-4586
1059-1524
DOI: 10.1091/mbc.e15-12-0865
Popis: Phosphatidylethanolamine (PE) and cardiolipin have specific roles in the activity and assembly of the mitochondrial respiratory chain supercomplexes, respectively, whereas phosphatidylcholine is redundant. Nonmitochondrial PE can be transported into mitochondria, where it can fully substitute for the lack of mitochondrial PE biosynthesis.
Mitochondrial membrane phospholipid composition affects mitochondrial function by influencing the assembly of the mitochondrial respiratory chain (MRC) complexes into supercomplexes. For example, the loss of cardiolipin (CL), a signature non–bilayer-forming phospholipid of mitochondria, results in disruption of MRC supercomplexes. However, the functions of the most abundant mitochondrial phospholipids, bilayer-forming phosphatidylcholine (PC) and non–bilayer-forming phosphatidylethanolamine (PE), are not clearly defined. Using yeast mutants of PE and PC biosynthetic pathways, we show a specific requirement for mitochondrial PE in MRC complex III and IV activities but not for their formation, whereas loss of PC does not affect MRC function or formation. Unlike CL, mitochondrial PE or PC is not required for MRC supercomplex formation, emphasizing the specific requirement of CL in supercomplex assembly. Of interest, PE biosynthesized in the endoplasmic reticulum (ER) can functionally substitute for the lack of mitochondrial PE biosynthesis, suggesting the existence of PE transport pathway from ER to mitochondria. To understand the mechanism of PE transport, we disrupted ER–mitochondrial contact sites formed by the ERMES complex and found that, although not essential for PE transport, ERMES facilitates the efficient rescue of mitochondrial PE deficiency. Our work highlights specific roles of non–bilayer-forming phospholipids in MRC function and formation.
Databáze: OpenAIRE