scholarly journals The fusogenic lipid phosphatidic acid promotes the biogenesis of mitochondrial outer membrane protein Ugo1

2015 ◽  
Vol 210 (6) ◽  
pp. 951-960 ◽  
Author(s):  
F.-Nora Vögtle ◽  
Michael Keller ◽  
Asli A. Taskin ◽  
Susanne E. Horvath ◽  
Xue Li Guan ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Phosphatidic Acid ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Lithocholic Acid ◽  
Mitochondrial Protein ◽  
Phospholipid Composition ◽  
Mitochondrial Proteins ◽  
Mitochondrial Outer Membrane

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.

scholarly journals Outer membrane protein functions as integrator of protein import and DNA inheritance in mitochondria

2016 ◽  
Vol 113 (31) ◽  
pp. E4467-E4475 ◽  
Author(s):  
Sandro Käser ◽  
Silke Oeljeklaus ◽  
Jiří Týč ◽  
Sue Vaughan ◽  
Bettina Warscheid ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Protein Import ◽  
Mitochondrial Protein ◽  
In Vitro Assays ◽  
Mitochondrial Outer Membrane ◽  
Mitochondrial Genomes ◽  
Dual Function ◽  
Complex Assembly

Trypanosomatids are one of the earliest diverging eukaryotes that have fully functional mitochondria. pATOM36 is a trypanosomatid-specific essential mitochondrial outer membrane protein that has been implicated in protein import. Changes in the mitochondrial proteome induced by ablation of pATOM36 and in vitro assays show that pATOM36 is required for the assembly of the archaic translocase of the outer membrane (ATOM), the functional analog of the TOM complex in other organisms. Reciprocal pull-down experiments and immunofluorescence analyses demonstrate that a fraction of pATOM36 interacts and colocalizes with TAC65, a previously uncharacterized essential component of the tripartite attachment complex (TAC). The TAC links the single-unit mitochondrial genome to the basal body of the flagellum and mediates the segregation of the replicated mitochondrial genomes. RNAi experiments show that pATOM36, in line with its dual localization, is not only essential for ATOM complex assembly but also for segregation of the replicated mitochondrial genomes. However, the two functions are distinct, as a truncated version of pATOM36 lacking the 75 C-terminal amino acids can rescue kinetoplast DNA missegregation but not the lack of ATOM complex assembly. Thus, pATOM36 has a dual function and integrates mitochondrial protein import with mitochondrial DNA inheritance.

scholarly journals Mutations in Fis1 disrupt orderly disposal of defective mitochondria

2014 ◽  
Vol 25 (1) ◽  
pp. 145-159 ◽  
Author(s):  
Qinfang Shen ◽  
Koji Yamano ◽  
Brian P. Head ◽  
Sumihiro Kawajiri ◽  
Jesmine T. M. Cheung ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Protein ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Couple Stress ◽  
Mitochondrial Fission ◽  
Mitochondrial Outer Membrane ◽  
Related Protein ◽  
Degradation Processes ◽  
Mitochondrial Toxins

Mitochondrial fission is mediated by the dynamin-related protein Drp1 in metazoans. Drp1 is recruited from the cytosol to mitochondria by the mitochondrial outer membrane protein Mff. A second mitochondrial outer membrane protein, named Fis1, was previously proposed as recruitment factor, but Fis1−/− cells have mild or no mitochondrial fission defects. Here we show that Fis1 is nevertheless part of the mitochondrial fission complex in metazoan cells. During the fission cycle, Drp1 first binds to Mff on the surface of mitochondria, followed by entry into a complex that includes Fis1 and endoplasmic reticulum (ER) proteins at the ER–mitochondrial interface. Mutations in Fis1 do not normally affect fission, but they can disrupt downstream degradation events when specific mitochondrial toxins are used to induce fission. The disruptions caused by mutations in Fis1 lead to an accumulation of large LC3 aggregates. We conclude that Fis1 can act in sequence with Mff at the ER–mitochondrial interface to couple stress-induced mitochondrial fission with downstream degradation processes.

scholarly journals Multispan mitochondrial outer membrane protein Ugo1 follows a unique Mim1-dependent import pathway

2011 ◽  
Vol 194 (3) ◽  
pp. 397-405 ◽  
Author(s):  
Dražen Papić ◽  
Katrin Krumpe ◽  
Jovana Dukanovic ◽  
Kai S. Dimmer ◽  
Doron Rapaport
Keyword(s):  
Membrane Protein ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Gel Electrophoresis ◽  
Mitochondrial Outer Membrane ◽  
Yeast Mitochondria ◽  
Membrane Complex ◽  
Native Gel ◽  
Insertion Process ◽  
Import Receptor

The mitochondrial outer membrane (MOM) harbors several multispan proteins that execute various functions. Despite their importance, the mechanisms by which these proteins are recognized and inserted into the outer membrane remain largely unclear. In this paper, we address this issue using yeast mitochondria and the multispan protein Ugo1. Using a specific insertion assay and analysis by native gel electrophoresis, we show that the import receptor Tom70, but not its partner Tom20, is involved in the initial recognition of the Ugo1 precursor. Surprisingly, the import pore formed by the translocase of the outer membrane complex appears not to be required for the insertion process. Conversely, the multifunctional outer membrane protein mitochondrial import 1 (Mim1) plays a central role in mediating the insertion of Ugo1. Collectively, these results suggest that Ugo1 is inserted into the MOM by a novel pathway in which Tom70 and Mim1 contribute to the efficiency and selectivity of the process.

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