Multifaceted roles of porin in mitochondrial protein and lipid transport

2019 ◽  
Vol 47 (5) ◽  
pp. 1269-1277 ◽  
Author(s):  
Toshiya Endo ◽  
Haruka Sakaue
Keyword(s):  
Outer Membrane ◽  
Protein Import ◽  
Mitochondrial Protein ◽  
Anion Channel ◽  
Lipid Transport ◽  
Mitochondrial Proteins ◽  
Carrier Protein ◽  
Intermembrane Space ◽  
Voltage Dependent Anion Channel ◽  
Tom Complex

Abstract Mitochondria are essential eukaryotic organelles responsible for primary cellular energy production. Biogenesis, maintenance, and functions of mitochondria require correct assembly of resident proteins and lipids, which require their transport into and within mitochondria. Mitochondrial normal functions also require an exchange of small metabolites between the cytosol and mitochondria, which is primarily mediated by a metabolite channel of the outer membrane (OM) called porin or voltage-dependent anion channel. Here, we describe recently revealed novel roles of porin in the mitochondrial protein and lipid transport. First, porin regulates the formation of the mitochondrial protein import gate in the OM, the translocase of the outer membrane (TOM) complex, and its dynamic exchange between the major form of a trimer and the minor form of a dimer. The TOM complex dimer lacks a core subunit Tom22 and mediates the import of a subset of mitochondrial proteins while the TOM complex trimer facilitates the import of most other mitochondrial proteins. Second, porin interacts with both a translocating inner membrane (IM) protein like a carrier protein accumulated at the small TIM chaperones in the intermembrane space and the TIM22 complex, a downstream translocator in the IM for the carrier protein import. Porin thereby facilitates the efficient transfer of carrier proteins to the IM during their import. Third, porin facilitates the transfer of lipids between the OM and IM and promotes a back-up pathway for the cardiolipin synthesis in mitochondria. Thus, porin has roles more than the metabolite transport in the protein and lipid transport into and within mitochondria, which is likely conserved from yeast to human.

Porins as helpers in mitochondrial protein translocation

2020 ◽  
Vol 401 (6-7) ◽  
pp. 699-708 ◽  
Author(s):  
Alexander Grevel ◽  
Thomas Becker
Keyword(s):  
Outer Membrane ◽  
Protein Import ◽  
Protein Translocation ◽  
Mitochondrial Protein ◽  
Anion Channel ◽  
Intermembrane Space ◽  
Voltage Dependent Anion Channel ◽  
Entry Site ◽  
Inner Membrane ◽  
Tom Complex

AbstractMitochondria import the vast majority of their proteins via dedicated protein machineries. The translocase of the outer membrane (TOM complex) forms the main entry site for precursor proteins that are produced on cytosolic ribosomes. Subsequently, different protein sorting machineries transfer the incoming preproteins to the mitochondrial outer and inner membranes, the intermembrane space, and the matrix. In this review, we highlight the recently discovered role of porin, also termed voltage-dependent anion channel (VDAC), in mitochondrial protein biogenesis. Porin forms the major channel for metabolites and ions in the outer membrane of mitochondria. Two different functions of porin in protein translocation have been reported. First, it controls the formation of the TOM complex by modulating the integration of the central receptor Tom22 into the mature translocase. Second, porin promotes the transport of carrier proteins toward the carrier translocase (TIM22 complex), which inserts these preproteins into the inner membrane. Therefore, porin acts as a coupling factor to spatially coordinate outer and inner membrane transport steps. Thus, porin links metabolite transport to protein import, which are both essential for mitochondrial function and biogenesis.

scholarly journals Cooperation of translocase complexes in mitochondrial protein import

2007 ◽  
Vol 179 (4) ◽  
pp. 585-591 ◽  
Author(s):  
Stephan Kutik ◽  
Bernard Guiard ◽  
Helmut E. Meyer ◽  
Nils Wiedemann ◽  
Nikolaus Pfanner
Keyword(s):  
Outer Membrane ◽  
Protein Import ◽  
Protein Complexes ◽  
Mitochondrial Protein ◽  
Mitochondrial Proteins ◽  
Intermembrane Space ◽  
Mitochondrial Protein Import ◽  
Inner Membrane ◽  
Precursor Proteins ◽  
Preprotein Translocation

Most mitochondrial proteins are synthesized in the cytosol and imported into one of the four mitochondrial compartments: outer membrane, intermembrane space, inner membrane, and matrix. Each compartment contains protein complexes that interact with precursor proteins and promote their transport. These translocase complexes do not act as independent units but cooperate with each other and further membrane complexes in a dynamic manner. We propose that a regulated coupling of translocases is important for the coordination of preprotein translocation and efficient sorting to intramitochondrial compartments.

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 Mitochondrial Protein Import

2004 ◽  
Vol 279 (44) ◽  
pp. 45701-45707 ◽  
Author(s):  
Masatoshi Esaki ◽  
Hidaka Shimizu ◽  
Tomoko Ono ◽  
Hayashi Yamamoto ◽  
Takashi Kanamori ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Protein Import ◽  
Protein Translocation ◽  
Mitochondrial Protein ◽  
Intermembrane Space ◽  
Outer Mitochondrial Membrane ◽  
Mitochondrial Protein Import ◽  
Tom Complex ◽  
Membrane Complex ◽  
Cytosolic Side

Protein translocation across the outer mitochondrial membrane is mediated by the translocator called the TOM (translocase of the outer mitochondrial membrane) complex. The TOM complex possesses two presequence binding sites on the cytosolic side (thecissite) and on the intermembrane space side (thetranssite). Here we analyzed the requirement of presequence elements and subunits of the TOM complex for presequence binding to thecisandtranssites of the TOM complex. The N-terminal 14 residues of the presequence of subunit 9 of F0-ATPase are required for binding to thetranssite. The interaction between the presequence and thecissite is not sufficient to anchor the precursor protein to the TOM complex. Tom7 constitutes or is close to thetranssite and has overlapping functions with the C-terminal intermembrane space domain of Tom22 in the mitochondrial protein import.

scholarly journals Role of the intermembrane-space domain of the preprotein receptor Tom22 in protein import into mitochondria.

1996 ◽  
Vol 16 (8) ◽  
pp. 4035-4042 ◽  
Author(s):  
D A Court ◽  
F E Nargang ◽  
H Steiner ◽  
R S Hodges ◽  
W Neupert ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Protein Import ◽  
Protein Translocation ◽  
Specific Binding ◽  
Mitochondrial Outer Membrane ◽  
Intermembrane Space ◽  
Inner Membrane ◽  
Terminal Domain ◽  
Tom Complex

Tom22 is an essential component of the protein translocation complex (Tom complex) of the mitochondrial outer membrane. The N-terminal domain of Tom22 functions as a preprotein receptor in cooperation with Tom20. The role of the C-terminal domain of Tom22, which is exposed to the intermembrane space (IMS), in its own assembly into the Tom complex and in the import of other preproteins was investigated. The C-terminal domain of Tom22 is not essential for the targeting and assembly of this protein, as constructs lacking part or all of the IMS domain became imported into mitochondria and assembled into the Tom complex. Mutant strains of Neurospora expressing the truncated Tom22 proteins were generated by a novel procedure. These mutants displayed wild-type growth rates, in contrast to cells lacking Tom22, which are not viable. The import of proteins into the outer membrane and the IMS of isolated mutant mitochondria was not affected. Some but not all preproteins destined for the matrix and inner membrane were imported less efficiently. The reduced import was not due to impaired interaction of presequences with their specific binding site on the trans side of the outer membrane. Rather, the IMS domain of Tom22 appears to slightly enhance the efficiency of the transfer of these preproteins to the import machinery of the inner membrane.

Multiple pathways for mitochondrial protein traffic

2009 ◽  
Vol 390 (8) ◽  
Author(s):  
Toshiya Endo ◽  
Koji Yamano
Keyword(s):  
Outer Membrane ◽  
Protein Trafficking ◽  
Protein Import ◽  
Mitochondrial Protein ◽  
Intermembrane Space ◽  
Mitochondrial Protein Import ◽  
Inner Membrane ◽  
Protein Traffic

Abstract Mitochondria are two-membrane bounded organelles consisting of 1000–2000 different proteins, most of which are synthesized in the cytosol and subsequently imported into mitochondria. The imported proteins are further sorted to one of the four compartments, the outer membrane, intermembrane space, inner membrane, and matrix, mostly following one of the five major pathways. Mitochondrial protein import and sorting are mediated by the translocator complexes in the membranes and chaperones in the aqueous compartments operating along the import pathways. Here, we summarize the expanding knowledge on the roles of translocators, chaperones, and related components in the multiple pathways for mitochondrial protein trafficking.

scholarly journals The intermembrane space protein Mix23 is a novel stress-induced mitochondrial import factor

2020 ◽  
Vol 295 (43) ◽  
pp. 14686-14697 ◽  
Author(s):  
Eva Zöller ◽  
Janina Laborenz ◽  
Lena Krämer ◽  
Felix Boos ◽  
Markus Räschle ◽  
...  
Keyword(s):  
Protein Import ◽  
Mitochondrial Protein ◽  
Mitochondrial Proteins ◽  
Temperature Sensitive ◽  
Intermembrane Space ◽  
Mitochondrial Import ◽  
Induced Stress ◽  
Evolutionarily Conserved ◽  
Precursor Proteins ◽  
Biogenesis Of Mitochondria

The biogenesis of mitochondria requires the import of hundreds of precursor proteins. These proteins are transported post-translationally with the help of chaperones, meaning that the overproduction of mitochondrial proteins or the limited availability of chaperones can lead to the accumulation of cytosolic precursor proteins. This imposes a severe challenge to cytosolic proteostasis and triggers a specific transcription program called the mitoprotein-induced stress response, which activates the proteasome system. This coincides with the repression of mitochondrial proteins, including many proteins of the intermembrane space. In contrast, herein we report that the so-far-uncharacterized intermembrane space protein Mix23 is considerably up-regulated when mitochondrial import is perturbed. Mix23 is evolutionarily conserved and a homolog of the human protein CCDC58. We found that, like the subunits of the proteasome, Mix23 is under control of the transcription factor Rpn4. It is imported into mitochondria by the mitochondrial disulfide relay. Mix23 is critical for the efficient import of proteins into the mitochondrial matrix, particularly if the function of the translocase of the inner membrane 23 is compromised such as in temperature-sensitive mutants of Tim17. Our observations identify Mix23 as a novel regulator or stabilizer of the mitochondrial protein import machinery that is specifically up-regulated upon mitoprotein-induced stress conditions.

scholarly journals Assembly of the Mitochondrial Protein Import Channel

2010 ◽  
Vol 21 (18) ◽  
pp. 3106-3113 ◽  
Author(s):  
Thomas Becker ◽  
Bernard Guiard ◽  
Nicolas Thornton ◽  
Nicole Zufall ◽  
David A. Stroud ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Protein Import ◽  
Mitochondrial Protein ◽  
Membrane Insertion ◽  
Outer Mitochondrial Membrane ◽  
Mitochondrial Protein Import ◽  
Transmembrane Segments ◽  
Tom Complex ◽  
Assembly Pathway ◽  
Assembly Defect

The preprotein translocase of the outer mitochondrial membrane (TOM) consists of a central β-barrel channel, Tom40, and six proteins with α-helical transmembrane segments. The precursor of Tom40 is imported from the cytosol by a pre-existing TOM complex and inserted into the outer membrane by the sorting and assembly machinery (SAM). Tom40 then assembles with α-helical Tom proteins to the mature TOM complex. The outer membrane protein Mim1 promotes membrane insertion of several α-helical Tom proteins but also affects the biogenesis of Tom40 by an unknown mechanism. We have identified a novel intermediate in the assembly pathway of Tom40, revealing a two-stage interaction of the precursor with the SAM complex. The second SAM stage represents assembly of Tom5 with the precursor of Tom40. Mim1-deficient mitochondria accumulate Tom40 at the first SAM stage like Tom5-deficient mitochondria. Tom5 promotes formation of the second SAM stage and thus suppresses the Tom40 assembly defect of mim1Δ mitochondria. We conclude that the assembly of newly imported Tom40 is directly initiated at the SAM complex by its association with Tom5. The involvement of Mim1 in Tom40 biogenesis can be largely attributed to its role in import of Tom5.

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 The Omp85 family of proteins is essential for outer membrane biogenesis in mitochondria and bacteria

2003 ◽  
Vol 164 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Ian Gentle ◽  
Kipros Gabriel ◽  
Peter Beech ◽  
Ross Waller ◽  
Trevor Lithgow
Keyword(s):  
Outer Membrane ◽  
Protein Import ◽  
Mitochondrial Fission ◽  
Anion Channel ◽  
Mitochondrial Outer Membrane ◽  
Organelle Biogenesis ◽  
Voltage Dependent Anion Channel ◽  
Protein Insertion ◽  
Outer Membrane Biogenesis ◽  
Integral Proteins

Integral proteins in the outer membrane of mitochondria control all aspects of organelle biogenesis, being required for protein import, mitochondrial fission, and, in metazoans, mitochondrial aspects of programmed cell death. How these integral proteins are assembled in the outer membrane had been unclear. In bacteria, Omp85 is an essential component of the protein insertion machinery, and we show that members of the Omp85 protein family are also found in eukaryotes ranging from plants to humans. In eukaryotes, Omp85 is present in the mitochondrial outer membrane. The gene encoding Omp85 is essential for cell viability in yeast, and conditional omp85 mutants have defects that arise from compromised insertion of integral proteins like voltage-dependent anion channel (VDAC) and components of the translocase in the outer membrane of mitochondria (TOM) complex into the mitochondrial outer membrane.

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