Hostname: page-component-669899f699-tpknm Total loading time: 0 Render date: 2025-04-25T18:45:33.187Z Has data issue: false hasContentIssue false
  • English
  • Français

Mitochondrial assembly: protein import

Published online by Cambridge University Press:  05 March 2007

David A. Hood  and
Anna-Maria Joseph
David A. Hood*
Affiliation:
School of Kinesiology and Health Science and Department of Biology, York University, Toronto, Ontario M3J 1P3, Canada
Anna-Maria Joseph
Affiliation:
School of Kinesiology and Health Science and Department of Biology, York University, Toronto, Ontario M3J 1P3, Canada
*
*Corresponding author: Dr David A. Hood Fax: +1 416 736 5698, Email: dhood@yorku.ca
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The protein import process of mitochondria is vital for the assembly of the hundreds of nuclear-derived proteins into an expanding organelle reticulum. Most of our knowledge of this complex multisubunit network comes from studies of yeast and fungal systems, with little information known about the protein import process in mammalian cells, particularly skeletal muscle. However, growing evidence indicates that the protein import machinery can respond to changes in the energy status of the cell. In particular, contractile activity, a powerful inducer of mitochondrial biogenesis, has been shown to alter the stoichiometry of the protein import apparatus via changes in several protein import machinery components. These adaptations include the induction of cytosolic molecular chaperones that transport precursors to the matrix, the up-regulation of outer membrane import receptors, and the increase in matrix chaperonins that facilitate the import and proper folding of the protein for subsequent compartmentation in the matrix or inner membrane. The physiological importance of these changes is an increased capacity for import into the organelle at any given precursor concentration. Defects in the protein import machinery components have been associated with mitochondrial disorders. Thus, contractile activity may serve as a possible mechanism for up-regulation of mitochondrial protein import and compensation for mitochondrial phenotype alterations observed in diseased muscle.

Keywords

Skeletal muscleExerciseProtein importMitochondrial disease
Type
Symposium 3: Mechanisms involved in exercise-induced mitochondrila biogenesis in skeletal muscle
Information
Proceedings of the Nutrition Society , Volume 63 , Issue 2 , May 2004 , pp. 293 - 300
Copyright
Copyright © The Nutrition Society 2004

References

Abe, Y, Shodai, T, Muto, T, Mihara, K, Torii, H, Nishikawa, S, Endo, T & Kohda, D (2000) Structural basis of presequence recognition by the mitochondrial import receptor Tom20. Cell 100, 551–560.Google Scholar
Aithal, HN & Tustanoff, ER (1975) Assembly of complex III into newly developing mitochondrial membranes. Canadian Journal of Biochemistry 53, 1278–1281.Google Scholar
Carrier, H, Flocard, F, Tagliati, V, Arrigo, AP & Godinot, C (2000) Immunolabelling of mitochondrial superoxide dismutase and of Hsp60 in muscles harbouring a respiratory chain deficiency. Neuromuscular Disorders 10, 144–149.Google Scholar
Chewawiwat, N, Yano, M, Terada, K, Hoogenraad, NJ & Mori, M (1999) Characterization of the novel mitochondrial protein import component, Tom34, in mammalian cells. Journal of Biochemistry (Tokyo) 125, 721–727.Google Scholar
Cogswell, AM, Stevens, RJ & Hood, DA (1993) Properties of skeletal muscle mitochondria isolated from subsarcolemmal and intermyofibrillar regions. American Journal of Physiology 264, C383–C389.Google Scholar
Colavecchia, M, Christie, LN, Kanwar, YS & Hood, DA (2003) Functional consequences of thyroid hormone-induced changes in the mitochondrial protein import pathway. American Journal of Physiology 284, E29–E35.Google Scholar
Craig, EE, Chesley, A & Hood, DA (1998) Thyroid hormone modifies mitochondrial phenotype by increasing protein import without altering degradation. American Journal of Physiology 275, C1508–C1515.Google Scholar
Dekker, PJ, Ryan, MT, Brix, J, Muller, H, Honlinger, A & Pfanner, N (1998) Preprotein translocase of the outer mitochondrial membrane: molecular dissection and assembly of the general import pore complex. Molecular and Cellular Biology 18, 6515–6524.Google Scholar
Desjardins, P, Frost, E & Morais, R (1985) Ethidium bromide-induced loss of mitochondrial DNA from primary chicken embryo fibroblasts. Molecular and Cellular Biology 5, 1163–1169.Google Scholar
Gakh, O, Cavadini, P & Isaya, G (2002) Mitochondrial processing peptidases. Biochimica et Biophysica Acta 1592, 63–77.Google Scholar
Geissler, A, Chacinska, A, Truscott, KN, Wiedemann, N, Brandner, K, Sickmann, A, Meyer, HE, Meisinger, C, Pfanner, N & Rehling, P (2002) The mitochondrial presequence translocase: an essential role of Tim50 in directing preproteins to the import channel. Cell 111, 507–518.Google Scholar
Goping, IS, Millar, DG & Shore, GC (1995) Identification of the human mitochondrial protein import receptor, huMas20p. Complementation of delta mas20 in yeast. FEBS Letters 373, 45–50.Google Scholar
Gordon, JW, Rungi, AA, Inagaki, H & Hood, DA (2001) Effects of contractile activity on mitochondrial transcription factor A expression in skeletal muscle. Journal of Applied Physiology 90, 389–396.Google Scholar
Grey, JY, Connor, MK, Gordon, JW, Yano, M, Mori, M & Hood, DA (2000) Tom20-mediated mitochondrial protein import in muscle cells during differentiation. American Journal of Physiology 279, C1393–C1400.Google Scholar
Hallman, M & Kankare, P (1971) Cardiolipin and cytochrome αα 3 in intact liver mitochondria of rats. Evidence of successive formation of inner membrane components. Biochemical and Biophysical Research Communications 45, 1004–1010.Google Scholar
Hernandez, JM, Giner, P & Hernandez-Yago, J (1999) Gene structure of the human mitochondrial outer membrane receptor Tom20 and evolutionary study of its family of processed pseudogenes. Gene 239, 283–291.Google Scholar
Herzberg, NH, Middelkoop, E, Adorf, M, Dekker, HL, Van Galen, MJ, Van den Berg, M, Bolhuis, PA & Van den Bogert, C (1993) Mitochondria in cultured human muscle cells depleted of mitochondrial DNA. European Journal of Cell Biology 61, 400–408.Google Scholar
Hofmann, S, Rothbauer, U, Muhlenbein, N, Neupert, W, Gerbitz, KD, Brunner, M & Bauer, MF (2002) The C66W mutation in the deafness dystonia peptide 1 (DDP1) affects the formation of functional DDP1.TIM13 complexes in the mitochondrial intermembrane space. Journal of Biological Chemistry 277, 23287–23293.Google Scholar
Hood, DA (2001) Contractile activity-induced mitochondrial biogenesis in skeletal muscle. Journal of Applied Physiology 90, 1137–1157.Google Scholar
Hoogenraad, NJ, Ward, LA & Ryan, MT (2002) Import and assembly of proteins into mitochondria of mammalian cells. Biochemica et Biophysica Acta 1592, 97–105.Google Scholar
Hoppeler, H (1986) Exercise-induced ultrastructural changes in skeletal muscle. International Journal of Sports Medicine 7, 187–204.Google Scholar
Irrcher, I, Adhihetty, PJ, Sheehan, T, Joseph, AM & Hood, DA (2003) PPARgamma coactivator-1alpha expression during thyroid hormone- and contractile activity-induced mitochondrial adaptations. America Journal of Physiology 284, C1669–C1677.Google Scholar
Isaya, G, Kalousek, F & Rosenberg, LE (1992) Amino-terminal octapeptides function as recognition signals for the mitochondrial intermediate peptidase. Journal of Biological Chemistry 267, 7904–7910.Google Scholar
Jamet-Vierny, C, Contamine, V, Boulay, J, Zickler, D & Picard, M (1997) Mutations in genes encoding the mitochondrial outer membrane proteins Tom70 and Mdm10 of Podospora anserina modify the spectrum of mitochondrial DNA rearrangements associated with cellular death. Molecular and Cellular Biology 17, 6359–6366.Google Scholar
Kalousek, F, Isaya, G & Rosenberg, LE (1992) Rat liver mitochondrial intermediate peptidase (MIP): purification and initial characterization. EMBO Journal 11, 2803–2809.Google Scholar
King, MP & Attardi, G (1989) Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation. Science 246, 500–503.Google Scholar
Koehler, CM, Jarosch, E, Tokatlidis, K, Schmid, K, Schweyen, RJ & Schatz, G (1998) Import of mitochondrial carriers mediated by essential proteins of the intermembrane space. Science 279, 369–373.Google Scholar
Koehler, CM, Leuenberger, D, Merchant, S, Renold, A, Junne, T & Schatz, G (1999) Human deafness dystonia syndrome is a mitochondrial disease. Proceedings of the National Academy of Sciences USA 96, 2141–2146.Google Scholar
Komiya, T, Sakaguchi, M & Mihara, K (1996) Cytoplasmic chaperones determine the targeting pathway of precursor proteins to mitochondria. EMBO Journal 15, 399–407.Google Scholar
Leenhouts, JM, Torok, Z, Mandieau, V, Goormaghtigh, E, de Kruijff, B (1996) The N-terminal half of a mitochondrial presequence peptide inserts into cardiolipin-containing membranes. Consequences for the action of a transmembrane potential. FEBS Letters 388, 34–38.Google Scholar
Leuenberger, D, Bally, NA, Schatz, G & Koehler, CM (1999) Different import pathways through the mitochondrial intermembrane space for inner membrane proteins. EMBO Journal 18, 4816–4822.Google Scholar
Martin, J, Mahlke, K & Pfanner, N (1991) Role of an energized inner membrane in mitochondrial protein import. Delta psi drives the movement of presequences. Journal of Biological Chemistry 266, 18051–18057.Google Scholar
Martinus, RD, Garth, GP, Webster, TL, Cartwright, P, Naylor, DJ, Hoj, PB & Hoogenraad, NJ (1996) Selective induction of mitochondrial chaperones in response to loss of the mitochondrial genome. European Journal of Biochemistry 240, 98–103.Google Scholar
Model, K, Meisinger, C, Prinz, T, Wiedemann, N, Truscott, KN, Pfanner, N & Ryan, MT (2001) Multistep assembly of the protein import channel of the mitochondrial outer membrane. Nature Structural Biology 8, 361–370.Google Scholar
Mokranjac, D, Paschen, SA, Kozany, C, Prokisch, H, Hoppins, SC, Nargang, FE, Neupert, W & Hell, K (2003) Tim50, a novel component of the TIM23 preprotein translocase of mitochondria. EMBO Journal 22, 816–825.Google Scholar
Nelson, N & Schatz, G (1979) Energy-dependent processing of cytoplasmically made precursors to mitochondrial proteins. Proceedings of the National Academy of Sciences USA 76, 4365–4369.Google Scholar
Neufer, PD, Ordway, GA, Hand, GA, Shelton, JM, Richardson, JA, Benjamin, IJ & Williams, RS (1996) Continuous contractile activity induces fiber type specific expression of HSP70 in skeletal muscle. American Journal of Physiology 271, C1828–C1837.CrossRefGoogle ScholarPubMed
Neupert, W (1997) Protein import into mitochondria. Annual Review of Biochemistry 66, 863–917.Google Scholar
Nuttall, SD, Hanson, BJ, Mori, M & Hoogenraad, NJ (1997) hTom34: a novel translocase for the import of proteins into human mitochondria. DNA and Cell Biology 16, 1067–1074.Google Scholar
Ornatsky, OI, Connor, MK & Hood, DA (1995) Expression of stress proteins and mitochondrial chaperonins in chronically stimulated skeletal muscle. Biochemical Journal 311, 119–123.Google Scholar
Pfanner, N & Geissler, A (2001) Versatility of the mitochondrial protein import machinery. Nature Reviews Molecular Cell Biology 2, 339–349.Google Scholar
Rassow, J, Maarse, AC, Krainer, E, Kubrich, M, Muller, H, Meijer, M, Craig, EA & Pfanner, N (1994) Mitochondrial protein import: biochemical and genetic evidence for interaction of matrix hsp70 and the inner membrane protein MIM44. Journal of Cell Biology 127, 1547–1556.Google Scholar
Rifai, Z, Welle, S, Kamp, C & Thornton, CA (1995) Ragged red fibers in normal aging and inflammatory myopathy. Annals of Neurology 37, 24–29.Google Scholar
Rothbauer, U, Hofmann, S, Muhlenbein, N, Paschen, SA, Gerbitz, KD, Neupert, W, Brunner, M & Bauer, MF (2001) Role of the deafness dystonia peptide 1 (DDP1) in import of human Tim23 into the inner membrane of mitochondria. Journal of Biological Chemistry 276, 37327–37334.Google Scholar
Rungi, AA, Primeau, A, Nunes Christie, L, Gordon, JW, Robinson, BH & Hood, DA (2001) Events upstream of mitochondrial protein import limit the oxidative capacity of fibroblasts in multiple mitochondrial disease. Biochimica et Biophysica Acta 1586, 146–154.Google Scholar
Scarpulla, RC (2002) Transcriptional activators and coactivators in the nuclear control of mitochondrial function in mammalian cells. Gene 286, 81–89.Google Scholar
Schneider, HC, Berthold, J, Bauer, MF, Dietmeier, K, Guiard, B, Brunner, M & Neupert, W (1994) Mitochondrial Hsp70/MIM44 complex facilitates protein import. Nature 371, 768–774.Google Scholar
Schneider, JJ & Hood, DA (2000) Effect of thyroid hormone on mtHsp70 expression, mitochondrial import and processing in cardiac muscle. Journal of Endocrinology 165, 9–17.Google Scholar
Seki, N, Moczko, M, Nagase, T, Zufall, N, Ehmann, B, Dietmeier, K, Schafer, E, Nomura, N & Pfanner, N (1995) A human homolog of the mitochondrial protein import receptor Mom19 can assemble with the yeast mitochondrial receptor complex. FEBS Letters 375, 307–310.Google Scholar
Sirrenberg, C, Endres, M, Folsch, H, Stuart, RA, Neupert, W & Brunner, M (1998) Carrier protein import into mitochondria mediated by the intermembrane proteins Tim10/Mrs11 and Tim12/Mrs5. Nature 391, 912–915.Google Scholar
Takahashi, M, Chesley, A, Freyssenet, D & Hood, DA (1998) Contractile activity-induced adaptations in the mitochondrial protein import system. American Journal of Physiology 274, C1380–C1387.Google Scholar
Takahashi, M & Hood, DA (1993) Chronic stimulation-induced changes in mitochondria and performance in rat skeletal muscle. Journal of Applied Physiology 74, 934–941.Google Scholar
Takahashi, M & Hood, DA (1996) Protein import into subsarcolemmal and intermyofibrillar skeletal muscle mitochondria. Differential import regulation in distinct subcellular regions. Journal of Biological Chemistry 271, 27285–27291.Google Scholar
Tiranti, V, Hoertnagel, K, Carrozzo, R, Galimberti, C, Munaro, M, Granatiero, M et al. (1998) Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency. American Journal of Human Genetics 63, 1609–1621.CrossRefGoogle ScholarPubMed
Truscott, KN, Brandner, K & Pfanner, N (2003) Mechanisms of protein import into mitochondria. Current Biology 13, R326–R337.Google Scholar
Van Wilpe, S, Ryan, MT, Hill, K, Maarse, AC, Meisinger, C, Brix, J, Dekker, PJ, Moczko, M, Wagner, R, Meijer, M, Guiard, B, Honlinger, A & Pfanner, N (1999) Tom22 is a multifunctional organizer of the mitochondrial preprotein translocase. Nature 401, 485–489.Google Scholar
Williams, RS, Salmons, S, Newsholme, EA, Kaufman, RE & Mellor, J (1986) Regulation of nuclear and mitochondrial gene expression by contractile activity in skeletal muscle. Journal of Biological Chemistry 261, 376–380.Google Scholar
Yamamoto, H, Esaki, M, Kanamori, T, Tamura, Y, Nishikawa, S & Endo, T (2002) Tim50 is a subunit of the TIM23 complex that links protein translocation across the outer and inner mitochondrial membranes. Cell 111, 519–528.Google Scholar
Yang, CS & Weiner, H (2002) Yeast two-hybrid screening identifies binding partners of human Tom34 that have ATPase activity and form a complex with Tom34 in the cytosol. Archives of Biochemistry and Biophysics 400, 105–110.Google Scholar
Young, JC, Hoogenraad, NJ & Hartl, FU (2003) Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the mitochondrial import receptor Tom70. Cell 112, 41–50.Google Scholar
Zeviani, M, Tiranti, V & Piantadosi, C (1998) Mitochondrial disorders. Medicine 77, 59–72.CrossRefGoogle ScholarPubMed