scholarly journals Characterization of mitochondrial outer membrane proteins involved in mitochondrial protein import in Trypanosoma brucei

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Shvetank Sharma ◽  
Ujjal K Singha ◽  
Minu Chaudhuri
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Trypanosoma Brucei ◽  
Protein Import ◽  
Outer Membrane Proteins ◽  
Mitochondrial Protein ◽  
Mitochondrial Outer Membrane ◽  
Mitochondrial Protein Import

scholarly journals Evolution of mitochondrial protein import – lessons from trypanosomes

2020 ◽  
Vol 401 (6-7) ◽  
pp. 663-676 ◽  
Author(s):  
André Schneider
Keyword(s):  
Membrane Protein ◽  
Outer Membrane ◽  
Protein Import ◽  
Outer Membrane Proteins ◽  
Mitochondrial Protein ◽  
Intermembrane Space ◽  
Mitochondrial Protein Import ◽  
System A ◽  
Import Receptors ◽  
Inner Membrane Protein

AbstractThe evolution of mitochondrial protein import and the systems that mediate it marks the boundary between the endosymbiotic ancestor of mitochondria and a true organelle that is under the control of the nucleus. Protein import has been studied in great detail in Saccharomyces cerevisiae. More recently, it has also been extensively investigated in the parasitic protozoan Trypanosoma brucei, making it arguably the second best studied system. A comparative analysis of the protein import complexes of yeast and trypanosomes is provided. Together with data from other systems, this allows to reconstruct the ancestral features of import complexes that were present in the last eukaryotic common ancestor (LECA) and to identify which subunits were added later in evolution. How these data can be translated into plausible scenarios is discussed, providing insights into the evolution of (i) outer membrane protein import receptors, (ii) proteins involved in biogenesis of α-helically anchored outer membrane proteins, and (iii) of the intermembrane space import and assembly system. Finally, it is shown that the unusual presequence-associated import motor of trypanosomes suggests a scenario of how the two ancestral inner membrane protein translocases present in LECA evolved into the single bifunctional one found in extant trypanosomes.

scholarly journals Mutant huntingtin does not cross the mitochondrial outer membrane

2020 ◽  
Vol 29 (17) ◽  
pp. 2962-2975
Author(s):  
James Hamilton ◽  
Tatiana Brustovetsky ◽  
Rajesh Khanna ◽  
Nickolay Brustovetsky
Keyword(s):  
Outer Membrane ◽  
Protein Import ◽  
Alkali Treatment ◽  
Mitochondrial Protein ◽  
Postmortem Brain ◽  
Mitochondrial Outer Membrane ◽  
Intermembrane Space ◽  
Mutant Huntingtin ◽  
Mitochondrial Protein Import ◽  
Brain Tissues

Abstract Mutant huntingtin (mHTT) is associated with mitochondria, but the exact mitochondrial location of mHTT has not been definitively established. Recently, it was reported that mHTT is present in the intermembrane space and inhibits mitochondrial protein import by interacting with TIM23, a major component of mitochondrial protein import machinery, but evidence for functional ramifications were not provided. We assessed mHTT location using synaptic and nonsynaptic mitochondria isolated from brains of YAC128 mice and subjected to alkali treatment or limited trypsin digestion. Mitochondria were purified either with discontinuous Percoll gradient or with anti-TOM22-conjugated iron microbeads. We also used mitochondria isolated from postmortem brain tissues of unaffected individuals and HD patients. Our results demonstrate that mHTT is located on the cytosolic side of the mitochondrial outer membrane (MOM) but does not cross it. This refutes the hypothesis that mHTT may interact with TIM23 and inhibit mitochondrial protein import. The levels of expression of nuclear-encoded, TIM23-transported mitochondrial proteins ACO2, TUFM, IDH3A, CLPP and mitochondrially encoded and synthesized protein mtCO1 were similar in mitochondria from YAC128 mice and their wild-type littermates as well as in mitochondria from postmortem brain tissues of unaffected individuals and HD patients, supporting the lack of deficit in mitochondrial protein import. Regardless of purification technique, mitochondria from YAC128 and WT mice had similar respiratory activities and mitochondrial membrane potentials. Thus, our data argue against mHTT crossing the MOM and entering into the mitochondrial intermembrane space, making it highly unlikely that mHTT interacts with TIM23 and inhibits protein import in intact mitochondria.

scholarly journals Procaspase-9 is attached to the mitochondrial outer membrane in the early stages of apoptosis

2007 ◽  
Vol 12 (4) ◽  
Author(s):  
Irina Milisav ◽  
Dušan Šuput
Keyword(s):  
Outer Membrane ◽  
Outer Surface ◽  
Protein Import ◽  
Mitochondrial Protein ◽  
Rat Hepatocytes ◽  
Mitochondrial Outer Membrane ◽  
Cell Type ◽  
Caspase 9 ◽  
Mitochondrial Protein Import ◽  
Cellular Location

AbstractProcaspase-9 is the zymogen form of one of the apoptosis initiators, caspase-9. Its cellular location may differ depending on the cell type; it is found throughout the cytosol, although some of it may be associated with the mitochondria. Procaspase-9 relocates from the cytosol to the mitochondria shortly after the triggering of apoptosis in rat hepatocytes. We investigated whether the mitochondrial protein import machineries import procaspase-9. The combined results of protein import analyses, mitochondrial fractionation and protease treatments of intact and swollen mitochondria imply that procaspase-9 attaches to the outer surface of the mitochondrial outer membrane.

Biogenesis pathways of α-helical mitochondrial outer membrane proteins

2020 ◽  
Vol 401 (6-7) ◽  
pp. 677-686 ◽  
Author(s):  
Layla Drwesh ◽  
Doron Rapaport
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Protein Import ◽  
Nuclear Dna ◽  
Current Knowledge ◽  
Outer Membrane Proteins ◽  
Mitochondrial Outer Membrane ◽  
Cytosolic Ribosomes

AbstractMitochondria harbor in their outer membrane (OM) proteins of different topologies. These proteins are encoded by the nuclear DNA, translated on cytosolic ribosomes and inserted into their target organelle by sophisticated protein import machineries. Recently, considerable insights have been accumulated on the insertion pathways of proteins into the mitochondrial OM. In contrast, little is known regarding the early cytosolic stages of their biogenesis. It is generally presumed that chaperones associate with these proteins following their synthesis in the cytosol, thereby keeping them in an import-competent conformation and preventing their aggregation and/or mis-folding and degradation. In this review, we outline the current knowledge about the biogenesis of different mitochondrial OM proteins with various topologies, and highlight the recent findings regarding their import pathways starting from early cytosolic events until their recognition on the mitochondrial surface that lead to their final insertion into the mitochondrial OM.

scholarly journals Structural Insight into Mitochondrial β-Barrel Outer Membrane Protein Biogenesis

2020 ◽  
Author(s):  
Kathryn A. Diederichs ◽  
Xiaodan Ni ◽  
Sarah E. Rollauer ◽  
Istvan Botos ◽  
Xiaofeng Tan ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Protein Import ◽  
Sequence Similarity ◽  
Outer Membrane Proteins ◽  
Complex Structure ◽  
Mitochondrial Outer Membrane ◽  
Intermembrane Space ◽  
Cytosolic Side ◽  
Lateral Gate

AbstractIn mitochondria, β-barrel outer membrane proteins mediate protein import, metabolite transport, lipid transport, and biogenesis. The Sorting and Assembly Machinery (SAM) complex consists of three proteins that assemble as a 1:1:1 complex to fold β-barrel proteins and insert them into the mitochondrial outer membrane. We report cryoEM structures of the SAM complex from Myceliophthora thermophila, which show that Sam50 forms a 16-stranded transmembrane β-barrel with a single polypeptide-transport-associated (POTRA) domain extending into the intermembrane space. Sam35 and Sam37 are located on the cytosolic side of the outer membrane, with Sam35 capping Sam50, and Sam37 interacting extensively with Sam35. Sam35 and Sam37 each adopt a GST-like fold, with no functional, structural, or sequence similarity to their bacterial counterparts. Structural analysis shows how the Sam50 β-barrel opens a lateral gate to accommodate its substrates. The SAM complex structure suggests how it interacts with other mitochondrial outer membrane proteins to create supercomplexes.

scholarly journals Role of Phosphatidylethanolamine in the Biogenesis of Mitochondrial Outer Membrane Proteins

2013 ◽  
Vol 288 (23) ◽  
pp. 16451-16459 ◽  
Author(s):  
Thomas Becker ◽  
Susanne E. Horvath ◽  
Lena Böttinger ◽  
Natalia Gebert ◽  
Günther Daum ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Outer Membrane Proteins ◽  
Proper Function ◽  
Mitochondrial Outer Membrane ◽  
Tom Complex ◽  
Precursor Proteins ◽  
Helical Proteins ◽  
The Stability

The mitochondrial outer membrane contains proteinaceous machineries for the import and assembly of proteins, including TOM (translocase of the outer membrane) and SAM (sorting and assembly machinery). It has been shown that the dimeric phospholipid cardiolipin is required for the stability of TOM and SAM complexes and thus for the efficient import and assembly of β-barrel proteins and some α-helical proteins of the outer membrane. Here, we report that mitochondria deficient in phosphatidylethanolamine (PE), the second non-bilayer-forming phospholipid, are impaired in the biogenesis of β-barrel proteins, but not of α-helical outer membrane proteins. The stability of TOM and SAM complexes is not disturbed by the lack of PE. By dissecting the import steps of β-barrel proteins, we show that an early import stage involving translocation through the TOM complex is affected. In PE-depleted mitochondria, the TOM complex binds precursor proteins with reduced efficiency. We conclude that PE is required for the proper function of the TOM complex.

Sign in / Sign up

Export Citation Format

Share Document