The fusogenic lipid phosphatidic acid promotes  the biogenesis of mitochondrial outer membrane  protein Ugo1.
Import and assembly of mitochondrial proteins depend on a complex interplay of proteinaceous translocation machineries. The role of lipids in this process has been studied only marginally and so far no direct role for a specific lipid in mitochondrial protein biogenesis has been shown. Here we analyzed a potential role of phosphatidic acid (PA) in biogenesis of mitochondrial proteins in Saccharomyces cerevisiae. In vivo remodeling of the mitochondrial lipid composition by lithocholic acid treatment or by ablation of the lipid transport protein Ups1, both leading to an increase of mitochondrial PA levels, specifically stimulated the biogenesis of the outer membrane protein Ugo1, a component of the mitochondrial fusion machinery. We reconstituted the import and assembly pathway of Ugo1 in protein-free liposomes, mimicking the outer membrane phospholipid composition, and found a direct dependency of Ugo1 biogenesis on PA. Thus, PA represents the first lipid that is directly involved in the biogenesis pathway of a mitochondrial membrane protein.
F-Nora
FN
Vögtle
Michael
M
Keller
Asli A
AA
Taskin
Susanne E
SE
Horvath
Xue Li
XL
Guan
Claudia
C
Prinz
Magdalena
M
Opalińska
Carina
C
Zorzin
Martin
M
van der Laan
Markus R
MR
Wenk
Rolf
R
Schubert
Nils
N
Wiedemann
Martin
M
Holzer
Chris
C
Meisinger
D008081:Liposomes; D008095:Lithocholic Acid / Q000494:pharmacology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D010712:Phosphatidic Acids / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D008081:Liposomes; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D010712:Phosphatidic Acids; D029701:Saccharomyces cerevisiae Proteins; C423986:UGO1 protein, S cerevisiae; C512497:Ups1 protein, S cerevisiae; D008095:Lithocholic Acid