Abstract:Tim23, a key component of the mitochondrial preprotein translocase, is anchored in the inner membrane by its C-terminal domain and exposes an intermediate domain in the intermembrane space that functions as a presequence receptor. We show that the N-terminal domain of Tim23 is exposed on the surface of the outer membrane. The two-membrane-spanning topology of Tim23 is a novel characteristic in membrane biology. By the simultaneous integration into two membranes, Tim23 forms contacts between the outer and inner… Show more
“…6a). Surprisingly, it has been reported that Tim23 is integrated into the outer membrane through its N-terminal domain 25 . Therefore, we investigated which domain of Tim23 forms the cation-selective channel identified here.…”
Section: Channel Formation By the C-terminal Domain Of Tim23mentioning
A presequence-and voltage-sensitive channel of the mitochondrial preprotein translocase formed by Tim23 Truscott, K.N.; Kovermann, P.; Geissler, A.; Merlin, A.; Driessen, Arnold; Rassow, J.; Pfanner, N.; Wagner, R.
“…6a). Surprisingly, it has been reported that Tim23 is integrated into the outer membrane through its N-terminal domain 25 . Therefore, we investigated which domain of Tim23 forms the cation-selective channel identified here.…”
Section: Channel Formation By the C-terminal Domain Of Tim23mentioning
A presequence-and voltage-sensitive channel of the mitochondrial preprotein translocase formed by Tim23 Truscott, K.N.; Kovermann, P.; Geissler, A.; Merlin, A.; Driessen, Arnold; Rassow, J.; Pfanner, N.; Wagner, R.
“…The TIM23 complex translocates preproteins with cleavable N -terminal presequences into the matrix or inner membrane, whereas the TIM22 complex is used by a subset of inner membrane proteins with internal import signals (5,68). Transfer of preproteins through both mitochondrial membranes occur at socalled translocation contact sites at which the outer and the inner boundary membrane come in close contact (69)(70)(71)(72). These translocation contact sites are formed on demand in a dynamic fashion between TOM and TIM23 or TIM22 complexes during the translocation of preproteins into the matrix or inner membrane ( Fig.…”
Section: Translocation Across the Inner Membranementioning
confidence: 99%
“…These translocation contact sites are formed on demand in a dynamic fashion between TOM and TIM23 or TIM22 complexes during the translocation of preproteins into the matrix or inner membrane ( Fig. 1) (71,(73)(74)(75)(76). Arrest of a matrix-targeted preprotein in such a way that it spans tightly both outer and inner membranes can form a stabilized translocation contact site.…”
Section: Translocation Across the Inner Membranementioning
confidence: 99%
“…The intermediate domain (amino acids »50-100) of the N-terminal half is localized in the intermembrane space and probably forms a presequence-receptor for preproteins (95). The N-terminal domain (amino acids »1-49) was recently shown to be integrated into the outer membrane (71). A small fragment of this domain can be clipped by protease added to intact isolated mitochondria.…”
Section: The Tim23 Complexmentioning
confidence: 99%
“…A small fragment of this domain can be clipped by protease added to intact isolated mitochondria. Thus, Tim23 appears to be a protein with a two-membranespanning topology, thereby providing a novel characteristic in membrane biology (71). Tim44 is a hydrophilic matrix protein, which is associated with the inner face of the inner membrane and can be released by high ionic strength or alkaline pH (86,96,97).…”
SummaryMost mitochondrial proteins are encoded by the nuclear genome and thus have to be imported into mitochondria from the cytosol. Protein translocation across and into the mitochondrial membranes is a multistep process facilitated by the coordinated action of at least four specialized translocation systems in the outer and inner membranes of mitochondria. The outer membrane contains one general translocase, the TOM complex, whereas three distinct translocases are located in the inner membrane, which facilitates translocation of different classes of preproteins. The TIM23 complex mediates import of matrix-targeted preproteins with Nterminal presequences, whereas hydrophobi c preproteins with internal targeting signals are inserted into the inner membrane via the TIM22 complex. The OXA translocase mediates the insertion of preproteins from the matrix space into the inner membrane. This review focuses on the structural organization and function of the import machinery of the model organisms of Saccharomyces cerevisiae and Neurospora crassa. In addition, the molecular basis of a new human mitochondrial disorder is discussed, the MohrTranebjaerg syndrome. This is the rst known disease, which is caused by an impaired mitochondrial protein import machinery leading to progressive neurodegeneration.
Sorted out! The proteins of mitochondria are provided by two different genetic systems. Following synthesis in the mitochondrial matrix or in the cytosol, they are specifically sorted into four mitochondrial compartments. The machineries, including the TOM complex (see picture), that direct the newly synthesized preproteins to their functional locations have been identified and are now studied in their molecular details.
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