The protein import apparatus of the mitochondrial outer membrane

1995 ◽  
Vol 73 (S1) ◽  
pp. 193-197 ◽  
Author(s):  
Deborah A. Court ◽  
Roland Lill ◽  
Walter Neupert
Keyword(s):  
Outer Membrane ◽  
Protein Import ◽  
Protein Complexes ◽  
Mitochondrial Outer Membrane ◽  
Intermembrane Space ◽  
Outer Membrane Receptor ◽  
Inner Membrane ◽  
Receptor Complexes ◽  
Entry Points ◽  
The Matrix

The majority of proteins within mitochondria are synthesized on cytosolic ribosomes and imported into the organelles. Protein complexes in the mitochondrial outer membrane harbour both the receptors that recognize these preproteins, and a translocation pore. These "receptor complexes" are the entry points for most preproteins, which are subsequently targeted to their final submitochondrial locations. The outer membrane complexes cooperate with the import machinery of the inner membrane to target preproteins to the inner membrane itself, the matrix, or, in some cases, to the intermembrane space. In isolated outer membranes, these complexes are capable of accurately importing preproteins destined for the outer membrane. Our current understanding of the composition, function, and biogenesis of these outer membrane receptor complexes is the focus of this article. Key words: mitochondria, outer membrane, protein import, receptors.

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.

scholarly journals The Taz1p Transacylase Is Imported and Sorted into the Outer Mitochondrial Membrane via a Membrane Anchor Domain

2013 ◽  
Vol 12 (12) ◽  
pp. 1600-1608 ◽  
Author(s):  
Jenny D. Herndon ◽  
Steven M. Claypool ◽  
Carla M. Koehler
Keyword(s):  
Outer Membrane ◽  
Point Mutations ◽  
Pathogenic Mutation ◽  
Barth Syndrome ◽  
Mitochondrial Outer Membrane ◽  
Intermembrane Space ◽  
Membrane Anchor ◽  
Inner Membrane ◽  
Content Type ◽  
The Matrix

ABSTRACT Mutations in the mitochondrial transacylase tafazzin, Taz1p, in Saccharomyces cerevisiae cause Barth syndrome, a disease of defective cardiolipin remodeling. Taz1p is an interfacial membrane protein that localizes to both the outer and inner membranes, lining the intermembrane space. Pathogenic point mutations in Taz1p that alter import and membrane insertion result in accumulation of monolysocardiolipin. In this study, we used yeast as a model to investigate the biogenesis of Taz1p. We show that to achieve this unique topology in mitochondria, Taz1p follows a novel import pathway in which it crosses the outer membrane via the translocase of the outer membrane and then uses the Tim9p-Tim10p complex of the intermembrane space to insert into the mitochondrial outer membrane. Taz1p is then transported to membranes of an intermediate density to reach a location in the inner membrane. Moreover, a pathogenic mutation within the membrane anchor (V224R) alters Taz1p import so that it bypasses the Tim9p-Tim10p complex and interacts with the translocase of the inner membrane, TIM23, to reach the matrix. Critical targeting information for Taz1p resides in the membrane anchor and flanking sequences, which are often mutated in Barth syndrome patients. These studies suggest that altering the mitochondrial import pathway of Taz1p may be important in understanding the molecular basis of Barth syndrome.

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.

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 Tim23–Tim50 pair coordinates functions of translocators and motor proteins in mitochondrial protein import

2009 ◽  
Vol 184 (1) ◽  
pp. 129-141 ◽  
Author(s):  
Yasushi Tamura ◽  
Yoshihiro Harada ◽  
Takuya Shiota ◽  
Koji Yamano ◽  
Kazuaki Watanabe ◽  
...  
Keyword(s):  
Motor Proteins ◽  
Protein Import ◽  
Protein Translocation ◽  
Mitochondrial Protein ◽  
Intermembrane Space ◽  
Mitochondrial Protein Import ◽  
Inner Membrane ◽  
The Matrix ◽  
General Protein ◽  
Mitochondrial Hsp70

Mitochondrial protein traffic requires coordinated operation of protein translocator complexes in the mitochondrial membrane. The TIM23 complex translocates and inserts proteins into the mitochondrial inner membrane. Here we analyze the intermembrane space (IMS) domains of Tim23 and Tim50, which are essential subunits of the TIM23 complex, in these functions. We find that interactions of Tim23 and Tim50 in the IMS facilitate transfer of precursor proteins from the TOM40 complex, a general protein translocator in the outer membrane, to the TIM23 complex. Tim23–Tim50 interactions also facilitate a late step of protein translocation across the inner membrane by promoting motor functions of mitochondrial Hsp70 in the matrix. Therefore, the Tim23–Tim50 pair coordinates the actions of the TOM40 and TIM23 complexes together with motor proteins for mitochondrial protein import.

scholarly journals Discrimination of distinct proteinases at the four structural levels of rat liver mitochondria

1986 ◽  
Vol 233 (1) ◽  
pp. 283-286 ◽  
Author(s):  
M C Duque-Magalhães ◽  
P Régnier
Keyword(s):  
Outer Membrane ◽  
Rat Liver ◽  
Degradation Products ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Intermembrane Space ◽  
Peptidase Activity ◽  
Inner Membrane ◽  
Mitochondrial Fractions ◽  
The Matrix

Rat liver mitochondrial fractions corresponding to four morphological structures (matrix, inner membrane, intermembrane space and outer membrane) contain proteinases that cleave casein components at different rates. Proteinases of the intermembrane space preferentially cleave kappa-casein, whereas the proteinases of the outer membrane, inner membrane and matrix fractions degrade alpha S1-casein more rapidly. Electrophoretic separation of the degradation products of alpha S1-casein and kappa-casein in polyacrylamide gels shows that different polypeptides are produced when the substrate is degraded by the matrix, by both membranes and by the intermembrane-space fraction. Some of the degradation products resulting from incubation of the caseins with the mitochondrial fractions are probably the result of digestion by contaminating lysosomal proteinase(s). The matrix has a high peptidase activity, since glucagon, a small peptide, is very rapidly degraded by this fraction. These observations strongly suggest that distinct proteinases, with different specificities, are associated respectively with the intermembrane space and with both membrane fractions.

scholarly journals Two Intermembrane Space Tim Complexes Interact with Different Domains of Tim23p during Its Import into Mitochondria

2000 ◽  
Vol 150 (6) ◽  
pp. 1271-1282 ◽  
Author(s):  
Alison J. Davis ◽  
Naresh B. Sepuri ◽  
Jason Holder ◽  
Arthur E. Johnson ◽  
Robert E. Jensen
Keyword(s):  
Protein Complexes ◽  
Intermediate Stage ◽  
Terminal Segment ◽  
Mitochondrial Outer Membrane ◽  
Cross Linking ◽  
Intermembrane Space ◽  
Cross Link ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane

Tim23p (translocase of the inner membrane) is an essential import component located in the mitochondrial inner membrane. To determine how the Tim23 protein itself is transported into mitochondria, we used chemical cross-linking to identify proteins adjacent to Tim23p during its biogenesis. In the absence of an inner membrane potential, Tim23p is translocated across the mitochondrial outer membrane, but not inserted into the inner membrane. At this intermediate stage, we find that Tim23p forms cross-linked products with two distinct protein complexes of the intermembrane space, Tim8p–Tim13p and Tim9p–Tim10p. Tim9p and Tim10p cross-link to the COOH-terminal domain of the Tim23 protein, which carries all of the targeting signals for Tim23p. Therefore, our results suggest that the Tim9p–Tim10p complex plays a key role in Tim23p import. In contrast, Tim8p and Tim13p cross-link to the hydrophilic NH2-terminal segment of Tim23p, which does not carry essential import information and, thus, the role of Tim8p–Tim13p is unclear. Tim23p contains two matrix-facing, positively charged loops that are essential for its insertion into the inner membrane. The positive charges are not required for interaction with the Tim9p–Tim10p complex, but are essential for cross-linking of Tim23p to components of the inner membrane insertion machinery, including Tim54p, Tim22p, and Tim12p.

scholarly journals Mutations in a tRNA Import Signal Define Distinct Receptors at the Two Membranes of LeishmaniaMitochondria

2000 ◽  
Vol 20 (19) ◽  
pp. 7410-7417 ◽  
Author(s):  
Subhendra Nath Bhattacharyya ◽  
Shankar Mukherjee ◽  
Samit Adhya
Keyword(s):  
Outer Membrane ◽  
Mitochondrial Matrix ◽  
Outer Membrane Receptor ◽  
Inner Membrane ◽  
Stem Loop ◽  
In Organello ◽  
The Matrix ◽  
Biochemical Fractionation ◽  
Membrane Transfer

ABSTRACT Nucleus-encoded tRNAs are selectively imported into the mitochondrion of Leishmania, a kinetoplastid protozoan. An oligoribonucleotide constituting the D stem-loop import signal of tRNATyr(GUA) was efficiently transported into the mitochondrial matrix in organello as well as in vivo. Transfer through the inner membrane could be uncoupled from that through the outer membrane and was resistant to antibody against the outer membrane receptor TAB. A number of mutations in the import signal had differential effects on outer and inner membrane transfer. Some mutants which efficiently traversed the outer membrane were unable to enter the matrix. Conversely, restoration of the loop-closing GC pair in reverse resulted in reversion of transfer through the inner, but not the outer, membrane, and binding of the RNA to the inner membrane was restored. These experiments indicate the presence at the two membranes of receptors with distinct specificities which mediate stepwise transfer into the mitochondrial matrix. The combination of oligonucleotide mutagenesis and biochemical fractionation may provide a general tool for the identification of tRNA transport factors.

scholarly journals Biogenesis of Mitochondrial Metabolite Carriers

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1008 ◽  
Author(s):  
Patrick Horten ◽  
Lilia Colina-Tenorio ◽  
Heike Rampelt
Keyword(s):  
Outer Membrane ◽  
Mitochondrial Outer Membrane ◽  
Intermembrane Space ◽  
Inner Membrane ◽  
Chaperone Function ◽  
Mitochondrial Inner Membrane ◽  
Metabolic Reactions ◽  
Almost All ◽  
Related Proteins ◽  
Shed Light

Metabolite carriers of the mitochondrial inner membrane are crucial for cellular physiology since mitochondria contribute essential metabolic reactions and synthesize the majority of the cellular ATP. Like almost all mitochondrial proteins, carriers have to be imported into mitochondria from the cytosol. Carrier precursors utilize a specialized translocation pathway dedicated to the biogenesis of carriers and related proteins, the carrier translocase of the inner membrane (TIM22) pathway. After recognition and import through the mitochondrial outer membrane via the translocase of the outer membrane (TOM) complex, carrier precursors are ushered through the intermembrane space by hexameric TIM chaperones and ultimately integrated into the inner membrane by the TIM22 carrier translocase. Recent advances have shed light on the mechanisms of TOM translocase and TIM chaperone function, uncovered an unexpected versatility of the machineries, and revealed novel components and functional crosstalk of the human TIM22 translocase.

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