Available online at www.sciencedirect.com
Biogenesis of mitochondrial membrane proteins
Thomas Becker1, Michael Gebert1,2, Nikolaus Pfanner1,3 and
Martin van der Laan1
Mitochondria are ubiquitous, double-membrane bound
organelles, which have developed from endosymbiotic
a-proteobacteria during evolution. Outer and inner membranes
of mitochondria are equipped with characteristic sets of
membrane proteins required for energy conversion, metabolite
and protein transport, membrane fusion and fission, and signal
transduction. Mitochondrial membrane proteins are encoded
by both, the nuclear and the mitochondrial genomes, and
exhibit divergent transmembrane topologies. Correct targeting
and membrane integration of these proteins and subsequent
assembly into functional protein complexes must be tightly
coordinated. This elaborate task is mediated by the
cooperative functions of different protein import and export
machineries of the outer and inner mitochondrial membranes.
Addresses
1
Institut für Biochemie und Molekularbiologie, ZMBZ, Universität
Freiburg, Stefan-Meier-Straße 17, D-79104 Freiburg, Germany
2
Fakultät für Biologie, Universität Freiburg, D-79104 Freiburg, Germany
3
Centre for Biological Signalling Studies (bioss), Universität Freiburg, D79104 Freiburg, Germany
Corresponding author: van der Laan,
Martin (martin.van.der.laan@biochemie.uni-freiburg.de)
Current Opinion in Cell Biology 2009, 21:484–493
This review comes from a themed issue on
Membranes and organelles
Edited by Greg Odorizzi and Peter Rehling
Available online 5th May 2009
0955-0674/$ – see front matter
# 2009 Elsevier Ltd. All rights reserved.
DOI 10.1016/j.ceb.2009.04.002
Introduction
Mitochondria are surrounded by two distinct membrane
systems, the outer membrane and the inner membrane,
that generate two internal aqueous compartments, intermembrane space and matrix. The inner membrane is
divided into peripheral regions adjacent to the outer
membrane (inner boundary membrane) and tube-like
invaginations protruding into the interior of the organelle
(cristae membrane) [1].
A comprehensive proteomic study with highly purified
Saccharomyces cerevisiae mitochondria has identified 850
different proteins [2]. Bioinformatics analysis of this data
set indicates that around 30% of these proteins are integral membrane proteins. The inner membrane contains
Current Opinion in Cell Biology 2009, 21:484–493
seven integral proteins that are encoded by mitochondrial
DNA and integrated into the membrane from the matrix
side. All other mitochondrial membrane proteins are
encoded in the nucleus and synthesized on cytosolic
ribosomes. These proteins have to be imported into
mitochondria and selectively integrated into the outer
membrane or inner membrane.
Integral membrane proteins are commonly classified
according to their transmembrane topology. While some
membrane proteins adopt a b-barrel transmembrane conformation, the majority span the lipid bilayer with one or
more hydrophobic a-helices. Proteins with a-helical
membrane-embedded domains are further distinguished
based on the number of transmembrane segments and
their position within the polypeptide sequence (C-tailanchored and signal-anchored). All these diverse topologies are found in mitochondrial membrane proteins
(Figure 1). Accordingly, diverse mitochondrial import
and assembly machineries of outer membrane, intermembrane space and inner membrane mediate the assembly of
different classes of membrane proteins.
Mitochondrial outer membrane proteins
Outer membrane proteins are required for metabolic
exchange and communication with the cytosol, membrane
fusion and fission and maintenance of mitochondrial
morphology. All nuclear-encoded proteins destined for
inner mitochondrial compartments initially have to pass
the outer membrane via the central entry gate, the translocase of the outer membrane (TOM complex) [1,3]. The
TOM complex is composed of the receptor proteins
Tom20, Tom70, and Tom22, the protein-conducting
channel formed by Tom40, and three small Tom proteins,
Tom5, Tom6 and Tom7, involved in complex stability and
dynamics. The outer membrane additionally contains the
sorting and assembly machinery (SAM complex), which is
required for the biogenesis of outer membrane proteins.
Tom40 and the SAM complex components Sam50 and
Sam35 are the only known mitochondrial outer membrane
proteins essential for cell viability in yeast.
All outer membrane proteins, including the Tom and Sam
subunits, are encoded by nuclear genes and synthesized
as precursors in the cytosol. Import and sorting of several
Tom and Sam precursors thus requires pre-existing mature TOM and SAM complexes.
b-Barrel proteins of the outer membrane
Characteristic for the outer membrane are proteins with a
b-barrel transmembrane structure, like Tom40 or porin.
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Mitochondrial membrane protein biogenesis Becker et al. 485
Figure 1
Major classes of mitochondrial membrane proteins. (a) Typical for the mitochondrial outer membrane is the presence of membrane proteins with a bbarrel transmembrane domain. Proteins, which are anchored to the outer membrane with a single a-helical transmembrane segment include two main
types, signal-anchored and C-tail-anchored proteins. Tom22 is inserted into the outer membrane with a topology comparable to that of C-tail
anchored proteins, yet additionally contains a domain in the intermembrane space (not shown). Furthermore, the outer membrane contains proteins
with multiple a-helical transmembrane segments (polytopic membrane proteins). (b) Mitochondrial inner membrane proteins are classified according
to type and position of their signal sequences. Proteins with N-terminal, cleavable signal sequences are either inserted into the inner membrane by a
single hydrophobic stop-transfer sequence or contain a polytopic transmembrane domain. Non-cleavable proteins with multiple, internal signal
sequences are mainly polytopic metabolite carriers.
These proteins are only found in the outer membrane of
Gram-negative bacteria and organelles of endosymbiotic
origin like plastids and mitochondria [3]. The biogenesis
pathway of b-barrel proteins has been conserved in evolution, as bacterial PhoE is assembled into the mitochondrial outer membrane when expressed in yeast [4]. bBarrel precursors are translocated across the outer membrane via the TOM complex and handed over to the SAM
complex by small Tim proteins of the intermembrane
space (Figure 2a) [5–8]. A specific motif in the last bstrand, the so-called b-signal, is crucial for binding of
precursor proteins to the SAM complex [9]. The SAM
complex mediates the membrane integration of b-barrel
precursors. Its core part (SAMcore) is composed of the
membrane-integral component Sam50 and two peripheral proteins, Sam35 and Sam37, exposed to the cytosolic
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side of the membrane (Figure 2a) [9,10]. Sam50 contains an N-terminal POTRA (polypeptide-transportassociated) domain and a C-terminal b-barrel domain.
This architecture is typical for proteins of the Omp85
(BamA/YaeT) family, which mediate membrane integration and assembly of b-barrel proteins in bacteria [3].
Recombinant Sam50 forms a transmembrane channel
with very similar electrophysiological properties as the
purified SAM complex [6,9].
Different views have been proposed on the mode of
precursor recognition by the SAM complex. One study
reported that the POTRA domain of Sam50 acts as a
receptor for the precursors of b-barrel proteins on the
intermembrane space side [11]. The multiple POTRA
domains of Omp85 (BamA/YaeT) are required for the
Current Opinion in Cell Biology 2009, 21:484–493
486 Membranes and organelles
Figure 2
Biogenesis of mitochondrial outer membrane proteins. (a) The precursors of b-barrel proteins are initially transferred across the outer membrane by
the TOM complex. The TOM complex consists of the receptor proteins Tom20, Tom70 and Tom22, the small Tom proteins Tom5, Tom6 and Tom7 and
the central, channel-forming component Tom40. Small Tim proteins of the intermembrane space take over b-barrel precursor proteins and deliver
them to the SAM complex, which mediates integration of these precursors into the outer membrane. Sam50 (Omp85/Tob55) and the two peripheral
subunits Sam35 and Sam37 form the SAMcore complex. Sam35 interacts with the b-signal of the incoming precursor. Mdm10 associates with SAMcore
to form the SAMholo complex, which is involved in the final steps of TOM complex assembly. (b) The SAM complex plays a central role in the assembly
of the TOM complex. Here, precursor proteins with different types of membrane anchors are assembled, leading to the formation of the functional
outer membrane translocase. The SAM machinery not only accepts the precursors of the b-barrel-forming Tom40 from the intermembrane space side,
but also the precursors of Tom22 and the small Tom proteins, which contain single a-helical transmembrane segments. Mim1 dynamically interacts
with SAM components to promote the biogenesis of the small Tom proteins. Mim1 is also crucial for the membrane integration and assembly of Tom20
and Tom70. Mdm10 mediates the association of Tom22 with Tom40 and the small Tom proteins.
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Mitochondrial membrane protein biogenesis Becker et al. 487
stability of the bacterial b-barrel assembly machinery
(BAM complex) and were also proposed to bind precursor
proteins [12,13]. In contrast to the POTRA domains of
bacterial homologs, however, the single POTRA domain
of Sam50 is not essential for cell viability [9]. Moreover,
Sam35 was shown to interact with b-signal sequences,
indicating that in mitochondria the Sam50 POTRA
domain is not solely responsible for substrate binding
and may even be dispensable for signal recognition [9]
(Figure 2a). This conclusion is supported by the observation that b-signal peptides stimulate channel activity of
the SAM complex, while the Sam50 channel alone does
not respond to signal peptide addition [9]. When precursor proteins are delivered to the SAM complex from
the intermembrane space whereas Sam35 is exposed on
the cytosolic side, how is substrate–receptor interaction
brought about? Electron microcopy images of both
recombinant Sam50 and purified SAM complexes show
large pentameric assemblies [6]. Moreover, SAM-bound
precursors reside in a hydrophilic environment within the
membrane [9]. Therefore, the most likely scenario is
that the SAM complex forms a central cavity in the outer
membrane allowing Sam35 to contact the precursor
protein. Such a cavity may also provide an appropriate
environment for the formation of b-barrels.
Sam37 plays a role in preprotein release from the SAM
complex, since overexpression of Sam37 promotes the
final stages of Tom40 assembly into mature TOM complexes [10]. A larger form of the SAM complex, termed
SAMholo, additionally contains Mdm10 (Figure 2a) [14].
Mdm10, which was initially identified as morphology
maintenance protein, is also required for late steps of
Tom40 biogenesis [14]. Mdm10 promotes the assembly
of Tom40 with further Tom proteins to form the oligomeric TOM complex. A second pool of Mdm10 is associated with the morphology proteins Mmm1 and Mdm12
[15]. This MDM complex is involved in late stages of bbarrel protein assembly [16]. A temperature-inducible
mmm1 mutant strain revealed that defects in b-barrel
biogenesis become detectable before morphology alterations [16]. Concordantly, deletion of outer membrane
biogenesis proteins, like Tom7 and Sam37, leads to
morphological changes [14,16]. These observations
indicate a close connection between outer membrane
protein biogenesis and mitochondrial morphology.
The three small Tom proteins are also involved in the late
steps of the assembly pathway of the Tom40 precursor.
Tom5 is the first Tom protein that stably associates with the
Tom40 precursor [5]. Tom6 and Tom7 then play antagonistic roles in the oligomeric assembly of the TOM complex.
Tom6 favors the formation of the TOM complex, whereas
Tom7 delays its formation. The exact molecular mechanism of Tom7 function is not yet known. It was shown that
Tom7 impairs the association of Mdm10 with the SAM
complex and thus regulates TOM assembly [17].
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a-Helical proteins of the outer membrane
Recent studies indicate that several pathways for the
import of a-helical outer membrane proteins exist, only
some of the pathways involve known TOM or SAM
components; the lipid composition of the membrane
may also be important [18,19,20,21]. For outer membrane proteins with one transmembrane segment the
membrane-spanning segment contains the mitochondrial
targeting signal. However, a general receptor for these
signals has not been found so far [22]. Recently, Tom70
was shown to recognize the polytopic outer membrane
protein peripheral benzodiazepine receptor [20]. This is
the first indication that a single Tom subunit may have a
function independently of the rest of the TOM complex.
Specific requirements have been reported for the biogenesis of TOM complex subunits with a single a-helical
transmembrane segment (Figure 2b). The TOM complex
itself is involved in mitochondrial targeting of the precursor of Tom22, but not of the tail-anchored small Tom
proteins [21,22]. Studies on the import pathways of
Tom22 and small Tom proteins revealed an unexpected
additional function of the SAM complex (Figure 2b). The
SAM complex is required for membrane integration of
Tom22 and involved in the assembly of small Tom
proteins into mature TOM complexes [19,23].
Mdm10 promotes the association of Tom22 and small
Tom proteins with Tom40 [14]. These findings suggest
that the SAM complex not only functions as membrane
insertase for b-barrel proteins but also for some a-helical
proteins. The SAM complex additionally provides an
assembly platform for the association of Tom precursors
into mature TOM complexes.
The SAM complex is not involved in the biogenesis of the
signal-anchored proteins Tom20 and Tom70 [19], but
the integral outer membrane protein Mim1 plays a central
role in membrane integration and assembly of these
precursors [23,24,25] (Figure 2b). Mim1 forms
homo-oligomers, which are required for Tom20 biogenesis [25]. Mim1 may perform the function of an
insertase for signal-anchored outer membrane proteins.
Mitochondrial inner membrane proteins
The mitochondrial inner membrane is one of the most
protein-rich membranes known (60–70 weight percent).
Many abundant inner membrane proteins are components of respiratory chain complexes or the F1Fo
ATP synthase, which accumulate in cristae membranes.
Moreover, the inner membrane contains preprotein translocase complexes, numerous metabolite carrier proteins
and representatives of other membrane protein families,
like ABC-transporters and AAA-proteases. Most of these
proteins are nuclear-encoded and imported as preproteins
from the cytosol. They contain specific signal sequences
directing them to the mitochondrial inner membrane.
Based on the type of import signal, two main classes of
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488 Membranes and organelles
Figure 3
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Mitochondrial membrane protein biogenesis Becker et al. 489
preproteins are distinguished: One is characterized by
multiple internal signals, whereas members of the other
contain N-terminal cleavable presequences.
Inner membrane proteins with internal signal
sequences
Inner membrane proteins with internal signal sequences
are mainly metabolite carriers or related proteins, like the
preprotein translocase subunits Tim17 and Tim23. Their
insertion into the inner membrane is mediated by the
carrier translocase of the inner membrane (TIM22 complex). On the surface of mitochondria, the multiple
import signals within carrier precursors are recognized
by several Tom70 molecules in a cooperative manner.
Passage of these precursor proteins across the outer
membrane is driven by their association with the
Tim9/Tim10 chaperone complex in the intermembrane
space (Figure 3a). The Tim9/Tim10 complex resembles a
six-bladed a-helical propeller, which binds and thus
shields hydrophobic patches in carrier precursors
[26,27]. A similar structure and binding mechanism
was described for the homologous Tim8/Tim13 complex,
which is involved in biogenesis of the Tim23 precursor
[28,29]. The Tim9/Tim10 complex delivers precursor
proteins to the TIM22 complex in a process involving the
docking protein Tim12 (Figure 3a). Interestingly, Tim12
associates first with Tim9 and Tim10 to form a soluble
docking complex, which subsequently binds to the membrane-embedded TIM22 complex [30].
The TIM22 complex migrates as a 300 kDa species on Blue
Native gels. This complex consists of the peripheral subunits Tim9, Tim10, Tim12, and the membrane-embedded
core formed by Tim22, Tim54, and Tim18 (Figure 3a) [31].
The essential Tim22 protein forms channels across the
inner membrane. The TIM22 complex contains two voltage-gated, signal sequence-sensitive channels, into which
pairs of transmembrane segments insert in a hairpin-like
conformation [31]. Tim54 is required for the stability of the
300 kDa complex and likely binds the Tim9/10/12 complex
[32]. Moreover, Tim54 was reported to have a specific role
in the biogenesis of the i-AAA protease component Yme1
[33]. Tim18 stimulates the assembly of the Tim54 precursor into TIM22 complexes [32]. The membrane potential (Dc) across the inner membrane is the only known
energy source for integration of carrier proteins into the
membrane. A low Dc is sufficient for the stable docking of
precursors to the TIM22 complex whereas membrane
integration of transmembrane segments requires a high
Dc [31].
Inner membrane proteins with N-terminal
presequences
Both, matrix-targeted and inner membrane-sorted preproteins with cleavable N-terminal presequences are
directly handed over from the TOM complex to the
presequence Translocase of the Inner Membrane
(TIM23 complex) via a two-membrane-spanning supercomplex intermediate. The membrane-embedded
TIM23 complex (TIM23CORE) consists of three essential
proteins: Tim17, Tim23 and Tim50 (Figure 3b). Tim23
and Tim50 interact via coiled-coil domains in the intermembrane space and are in close proximity to preproteins
emerging from the TOM complex [34,35,36]. Tim23
forms a voltage-dependent, preprotein-sensitive channel
across the inner membrane. In the absence of preproteins
the Tim23 channel is in a closed state. Tim50 is involved
in closing the channel in the absence of substrate
[37,38]. When a preprotein arrives, Tim50 binds to it
and likely initiates the reaction that induces channel
opening. The exact function of Tim17 is unknown; it
is required for matrix translocation as well as membrane
insertion of preproteins and appears to be involved in
regulation of the Tim23 channel [39–41].
TIM23CORE associates with an additional inner membrane
protein, Tim21, which contacts Tom22 in the outer membrane and is involved in transfer of preproteins from TOM
to TIM23 [39,42,43]. Tim21-containing TIM23 complexes (TIM23SORT) specifically associate with inner
membrane-sorted preproteins [39] (Figure 3b). Purification and functional reconstitution of TIM23SORT into
liposomes showed that this complex catalyzes membrane
insertion of cleavable inner membrane proteins that con-
Figure 3 Legend Biogenesis of mitochondrial inner membrane proteins. (a) Upon passage through the TOM complex in the outer membrane, carrier
precursors with multiple internal signal sequences are guided by the small Tim proteins (Tim9/Tim10 complex) through the aqueous environment of the
intermembrane space. A docking complex additionally containing Tim12 delivers the preprotein to the carrier translocase (TIM22 complex) in the inner
membrane. The TIM22 complex includes the central, pore-forming Tim22 protein and the accessory subunits Tim18 and Tim54. Membrane insertion of
carrier proteins via the TIM22 complex is driven by the electrical potential across the inner membrane (Dc). (b) Inner membrane proteins with Nterminal cleavable presequences are transferred across the outer membrane via the TOM complex. They are directly handed over to the presequence
translocase (TIM23 complex) in the inner membrane. The essential core of the TIM23 complex is formed by Tim23, Tim17, and Tim50. Presequence
proteins with a stop-transfer signal (indicated by a red box) adjacent to the N-terminal presequence are inserted into the inner membrane by the
TIM23SORT complex, which contains Tim21. The energy source for this process is the Dc. Tim21 connects TIM23SORT with two respiratory chain
complexes, cytochrome bc1 complex and cytochrome c oxidase (COX), probably via the bc1 subunit Qcr6. Biogenesis of more complex inner
membrane proteins, which contain multiple transmembrane segments and/or large matrix-domains, requires the TIM23MOTOR complex. This form of
the TIM23 complex is devoid of Tim21, but coupled to the ATP-driven presequence translocase-associated motor (PAM). The activity of the central
motor component mtHsp70 is regulated by four membrane-bound cochaperones, Pam18/Pam16 (Tim14/Tim16), Tim44 and Pam17. (c) A number of
particularly hydrophobic inner membrane proteins are encoded by the mitochondrial genome and synthesized on mitochondrial ribosomes in the
matrix. These proteins are co-translationally targeted to a protein export complex in the inner membrane that contains Oxa1. Biogenesis of
mitochondrially encoded proteins additionally involves Mba1, Mdm38, and Cox18 (Oxa2).
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Current Opinion in Cell Biology 2009, 21:484–493
490 Membranes and organelles
tain a single hydrophobic stop-transfer sequence [38]. Dc
is the sole energy source for this process. Surprisingly,
TIM23SORT was found in association with respiratory
chain complexes in mitochondria (Figure 3b)
[38,44,45,46]. This interaction is mediated by Tim21
and stimulates Dc-dependent membrane insertion of preproteins [44,45]. By an elegant fluorescence approach,
Alder et al. [47] have recently shown that transmembrane
segment 2 of Tim23 lines the transversal protein-conducting channel. It is, however, unknown, where and how
lateral gating of the TIM23 complex and release of transmembrane segments into the lipid bilayer occurs.
Biogenesis of proteins with C-terminal transmembrane
segments and polytopic membrane proteins is a more
complicated task. Translocation of preprotein domains
across the inner membrane requires the ATP-driven
Presequence translocase-Associated Motor (PAM)
(Figure 3b). The key component of this import motor
is the mitochondrial heat shock protein 70 (mtHsp70),
which generates an inward-directed import driving force.
Its activity is regulated in space and time by five cochaperones: Tim44, Pam16, Pam17, Pam18 and Mge1
[1]. Recruitment of PAM to TIM23 for matrix translocation (TIM23MOTOR) is accompanied by the release of
Tim21 from TIM23CORE [39]. In turn, binding of Tim21
to TIM23CORE drastically reduces its affinity for PAM
components. This is reflected by the fact that only minute
amounts of Tim21 are co-isolated with PAM components
and vice versa [38,39,44,48,49]. The precise signals
within preproteins that induce the transition between
TIM23SORT and TIM23MOTOR remain to be determined.
It has been proposed that presequence-carrying polytopic
inner membrane proteins are first translocated into the
matrix by TIM23MOTOR and subsequently integrated
into the membrane from the matrix side by an export
machinery containing Oxa1 (‘conservative sorting’)
[1,50]. Alternatively, the TIM23 complex may switch
between the matrix translocation and membrane integration states during the biogenesis of polytopic inner
membrane proteins. Evidence has been presented that
Oxa1 might accept transmembrane segments laterally
released from TIM23 within the membrane [51].
Mitochondrially encoded inner membrane
proteins
A small number of inner membrane proteins is encoded
by mitochondrial DNA. These proteins are strongly
hydrophobic subunits of the cytochrome bc1 complex,
cytochrome c oxidase, and F1Fo ATP synthase. Oxa1 is
believed to form the main insertase for proteins synthesized within mitochondria (Figure 3c). The molecular
nature of the protein-conducting export channel is
unknown. Purified Oxa1 forms homooligomeric complexes [52], which may constitute the core domain of
an insertion complex. Co-translational targeting of preCurrent Opinion in Cell Biology 2009, 21:484–493
proteins to Oxa1 involves binding of ribosomes to the Cterminal matrix domain [53,54]. Ribosome recruitment to
the inner membrane also involves Mdm38 and Mba1
[55,56] (Figure 3c). In case of the cytochrome c oxidase
subunit Cox2, Oxa1 is required for export of the Nterminus to the intermembrane space, while translocation
of the C-terminus depends on Cox18 [57,58] (Figure 3c).
An additional role for Oxa1 as an intramembrane chaperone in the assembly of the F1Fo ATP synthase has been
suggested [59].
Conclusions and perspectives
Diverse biogenesis pathways are involved in mitochondrial membrane protein insertion and assembly. Many
components have been discovered but we are only beginning to understand the molecular details underlying
different pathways. Further studies are required to elucidate the interaction of different outer membrane precursor proteins with the SAM complex and the
mechanisms of b-barrel and a-helix membrane integration. Yet unrecognized additional insertase complexes
for the insertion of a-helical membrane proteins may
exist in the outer membrane. The specific roles of different SAM complex forms and the MDM complex in the
assembly of b-barrel and a-helical proteins into functional outer membrane protein complexes remain to be
analyzed. For inner membrane protein biogenesis, it is
unclear, how the TIM23 machinery switches between
matrix translocation and inner membrane insertion.
Although the pore-forming components of the TIM22
and TIM23 complexes have been identified, we do not
know the molecular mechanism of how preproteins use
these channels to become inserted into the membrane. In
particular, the molecular nature of the putative lateral
gate releasing transmembrane segments from the translocase into the lipid phase of the membrane has remained
enigmatic. In all cases, our insight into the architecture
and function of membrane protein insertase complexes
will strongly benefit from high-resolution structures.
Finally, a number of recent studies indicated that the
role of particular phospholipids, such as cardiolipin, in the
biogenesis and dynamics of inner membrane protein
complexes might have been underestimated in the past.
Functional reconstitution of the TIM23SORT complex
into proteoliposomes requires a cardiolipin-rich membrane [38]. Moreover, two recent studies have shown
that a fraction of ADP/ATP carrier molecules is associated
with respiratory chain complexes [46,60] and that this
interaction depends on cardiolipin [60]. Finally, the
Tam41 protein, which was initially described as a specific
modulator of the TIM23 complex [48,61], was found to
play a crucial role in cardiolipin biosynthesis [62].
Acknowledgements
Work in the authors’ laboratories was supported by the Deutsche
Forschungsgemeinschaft, Sonderforschungsbereich 746, Excellence
Initiative of the German Federal & State Governments (EXC 294) and
Landesstiftung Baden-Württemberg (TB).
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Mitochondrial membrane protein biogenesis Becker et al. 491
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Current Opinion in Cell Biology 2009, 21:484–493
492 Membranes and organelles
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Current Opinion in Cell Biology 2009, 21:484–493
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www.sciencedirect.com
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Current Opinion in Cell Biology 2009, 21:484–493