TIM23 PAM complex translocates proteins from the mitochondrial intermembrane space to the mitochondrial matrix

Stable Identifier
Reaction [transition]
Saccharomyces cerevisiae
SVG |   | PPTX  | SBGN
TIM23 PAM complex translocates proteins from the mitochondrial intermembrane space to the mitochondrial matrix

The TIM23 complex transports precursor proteins across the inner membrane and into the matrix (Voisine et al. 2000, Mokranjac et al. 2003, Chacinska et al. 2005,Wiedemann et al. 2007, Hutu et al. 2008, Popov-Celeketic et al. 2008, Chacinska et al. 2010). Subunits TIM50, TIM17, and TIM23 are necessary for initiating translocation (Mokranjac et al.2003, Milisav et al. 2001) while the PAM complex with mtHSP70 (SSC1) provides the motive force that drives the transport (Milisav et al. 2001, Truscott et al. 2003, Frazier et al. 2004, D'Silva et al. 2005, van der Laan et al. 2005, Yamano et al. 2008). Hsp70 (mtHsp70, Ssc1) binding to the precursor pulls the protein into the matrix in a reaction requiring ATP hydrolysis (Gambill et al. 1993, Schneider et al. 1994, Kronidou et al. 1994, Ungermann et al. 1994, Voos et al. 1996, Voisine et al. 1999, Voisine et al. 2000, Krayl et al. 2007). The reaction appears to use a Brownian ratchet mechanism (Yamano et al. 2008).
Substrates of TIM23:PAM include Hsp60 (Gallas et al. 2006) and Yfh1 (Voisine et al. 2000).

Literature References
PubMed ID Title Journal Year
15797382 Mitochondrial presequence translocase: switching between TOM tethering and motor recruitment involves Tim21 and Tim17

Chacinska, A, Lind, M, Frazier, AE, Dudek, J, Meisinger, C, Geissler, A, Sickmann, A, Meyer, HE, Truscott, KN, Guiard, B, Pfanner, N, Rehling, P

Cell 2005
16107694 Pam17 is required for architecture and translocation activity of the mitochondrial protein import motor

van der Laan, M, Chacinska, A, Lind, M, Perschil, I, Sickmann, A, Meyer, HE, Guiard, B, Meisinger, C, Pfanner, N, Rehling, P

Mol Cell Biol 2005
21969381 Direct interaction of mitochondrial targeting presequences with purified components of the TIM23 protein complex

Marom, M, Dayan, D, Demishtein-Zohary, K, Mokranjac, D, Neupert, W, Azem, A

J Biol Chem 2011
14981507 Pam16 has an essential role in the mitochondrial protein import motor

Frazier, AE, Dudek, J, Guiard, B, Voos, W, Li, Y, Lind, M, Meisinger, C, Geissler, A, Sickmann, A, Meyer, HE, Bilanchone, V, Cumsky, MG, Truscott, KN, Pfanner, N, Rehling, P

Nat Struct Mol Biol 2004
8408191 A dual role for mitochondrial heat shock protein 70 in membrane translocation of preproteins

Gambill, BD, Voos, W, Kang, PJ, Miao, B, Langer, T, Craig, EA, Pfanner, N

J Cell Biol 1993
16105940 Role of Pam16's degenerate J domain in protein import across the mitochondrial inner membrane

D'Silva, PR, Schilke, B, Walter, W, Craig, EA

Proc Natl Acad Sci U S A 2005
17074805 A cooperative action of the ATP-dependent import motor complex and the inner membrane potential drives mitochondrial preprotein import

Krayl, M, Lim, JH, Martin, F, Guiard, B, Voos, W

Mol Cell Biol 2007
10779357 Role of the mitochondrial Hsp70s, Ssc1 and Ssq1, in the maturation of Yfh1

Voisine, C, Schilke, B, Ohlson, M, Beinert, H, Marszalek, J, Craig, EA

Mol Cell Biol 2000
7973708 The role of Hsp70 in conferring unidirectionality on protein translocation into mitochondria

Ungermann, C, Neupert, W, Cyr, DM

Science 1994
22298705 Genetic Analysis of Complex Interactions Amongst Components of the Mitochondrial Import Motor and Translocon in Saccharomyces cerevisiae

Schilke, BA, Hayashi, M, Craig, EA

Genetics 2012
18070913 Sorting switch of mitochondrial presequence translocase involves coupling of motor module to respiratory chain

Wiedemann, N, van der Laan, M, Hutu, DP, Rehling, P, Pfanner, N

J Cell Biol 2007
7809127 Dynamic interaction between Isp45 and mitochondrial hsp70 in the protein import system of the yeast mitochondrial inner membrane

Kronidou, NG, Oppliger, W, Bolliger, L, Hannavy, K, Glick, BS, Schatz, G, Horst, M

Proc Natl Acad Sci U S A 1994
19884344 Distinct forms of mitochondrial TOM-TIM supercomplexes define signal-dependent states of preprotein sorting

Chacinska, A, van der Laan, M, Mehnert, CS, Guiard, B, Mick, DU, Hutu, DP, Truscott, KN, Wiedemann, N, Meisinger, C, Pfanner, N, Rehling, P

Mol Cell Biol 2010
18418384 Active remodelling of the TIM23 complex during translocation of preproteins into mitochondria

Popov-Celeketi?, D, Mapa, K, Neupert, W, Mokranjac, D

EMBO J 2008
12574118 Tim50, a novel component of the TIM23 preprotein translocase of mitochondria

Mokranjac, D, Paschen, SA, Kozany, C, Prokisch, H, Hoppins, SC, Nargang, FE, Neupert, W, Hell, K

EMBO J 2003
8654364 Differential requirement for the mitochondrial Hsp70-Tim44 complex in unfolding and translocation of preproteins

Voos, W, von Ahsen, O, Müller, H, Guiard, B, Rassow, J, Pfanner, N

EMBO J 1996
18400944 Mitochondrial protein import motor: differential role of Tim44 in the recruitment of Pam17 and J-complex to the presequence translocase

Hutu, DP, Guiard, B, Chacinska, A, Becker, D, Pfanner, N, Rehling, P, van der Laan, M

Mol Biol Cell 2008
11344168 Modular structure of the TIM23 preprotein translocase of mitochondria

Milisav, I, Moro, F, Neupert, W, Brunner, M

J Biol Chem 2001
10367886 The protein import motor of mitochondria: unfolding and trapping of preproteins are distinct and separable functions of matrix Hsp70

Voisine, C, Craig, EA, Zufall, N, von Ahsen, O, Pfanner, N, Voos, W

Cell 1999
7935837 Mitochondrial Hsp70/MIM44 complex facilitates protein import

Schneider, HC, Berthold, J, Bauer, MF, Dietmeier, K, Guiard, B, Brunner, M, Neupert, W

Nature 1994
16790493 Characterization of Mmp37p, a Saccharomyces cerevisiae mitochondrial matrix protein with a role in mitochondrial protein import

Gallas, MR, Dienhart, MK, Stuart, RA, Long, RM

Mol Biol Cell 2006
18678864 Step-size analyses of the mitochondrial Hsp70 import motor reveal the Brownian ratchet in operation

Yamano, K, Kuroyanagi-Hasegawa, M, Esaki, M, Yokota, M, Endo, T

J Biol Chem 2008
7798311 Mitochondrial protein import: biochemical and genetic evidence for interaction of matrix hsp70 and the inner membrane protein MIM44

Rassow, J, Maarse, AC, Krainer, E, Kübrich, M, Müller, H, Meijer, M, Craig, EA, Pfanner, N

J Cell Biol 1994
14638855 A J-protein is an essential subunit of the presequence translocase-associated protein import motor of mitochondria

Truscott, KN, Voos, W, Frazier, AE, Lind, M, Li, Y, Geissler, A, Dudek, J, Müller, H, Sickmann, A, Meyer, HE, Meisinger, C, Guiard, B, Rehling, P, Pfanner, N

J Cell Biol 2003
Catalyst Activity

protein transmembrane transporter activity of TIM23 PAM:Cargo [mitochondrial inner membrane]

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