Multiple Pathways for Sorting Mitochondrial Precursor Proteins

Overview

Journal EMBO Rep

Specialty Molecular Biology

Date 2008 Jan 5

PMID 18174896

Citations 131

Authors

Natalia Bolender

Albert Sickmann

Richard Wagner

Chris Meisinger

Nikolaus Pfanner

Affiliations

Soon will be listed here.

Abstract

Mitochondria import hundreds of different precursor proteins from the cytosol. More than 50% of mitochondrial proteins do not use the classical import pathway that is guided by amino-terminal presequences, but instead contain different types of internal targeting signals. Recent studies have revealed an unexpected complexity of the mitochondrial protein import machinery and have led to the discovery of new transport pathways. Here, we review the versatility of mitochondrial protein import and its connection to mitochondrial morphology, redox regulation and energetics.

Citing Articles

Characterisation and comparative analysis of mitochondrial genomes of false, yellow, black and blushing morels provide insights on their structure and evolution.

Tao G, Ahrendt S, Miyauchi S, Zhu X, Peng H, Labutti K IMA Fungus. 2025; 16:e138363.

PMID: 40052075 PMC: 11881001. DOI: 10.3897/imafungus.16.138363.

NOTCH1 mitochondria localization during heart development promotes mitochondrial metabolism and the endothelial-to-mesenchymal transition in mice.

Wang J, Zhao R, Xu S, Zhou X, Cai K, Chen Y Nat Commun. 2024; 15(1):9945.

PMID: 39550366 PMC: 11569218. DOI: 10.1038/s41467-024-54407-7.

Discovery of novel disease-causing mutation in and its correction using adenine base editor to improve mitochondrial function.

Cha J, Lee S, Yun Y, Choi W, Koo H, Jung S Mol Ther Nucleic Acids. 2024; 35(3):102257.

PMID: 39104869 PMC: 11299580. DOI: 10.1016/j.omtn.2024.102257.

The Mitochondrial Connection: The Nek Kinases' New Functional Axis in Mitochondrial Homeostasis.

Basei F, E Silva I, Dias P, Ferezin C, Peres de Oliveira A, Issayama L Cells. 2024; 13(6.

PMID: 38534317 PMC: 10969439. DOI: 10.3390/cells13060473.

LARP4 is an RNA-binding protein that binds nuclear-encoded mitochondrial mRNAs to promote mitochondrial function.

Lewis B, Cho C, Her H, Mizrahi O, Hunter T, Yeo G RNA. 2024; 30(3):223-239.

PMID: 38164626 PMC: 10870378. DOI: 10.1261/rna.079799.123.

References

Geissler A, Chacinska A, Truscott K, Wiedemann N, Brandner K, Sickmann A . The mitochondrial presequence translocase: an essential role of Tim50 in directing preproteins to the import channel. Cell. 2002; 111(4):507-18. DOI: 10.1016/s0092-8674(02)01073-5. View

Li Y, Dudek J, Guiard B, Pfanner N, Rehling P, Voos W . The presequence translocase-associated protein import motor of mitochondria. Pam16 functions in an antagonistic manner to Pam18. J Biol Chem. 2004; 279(36):38047-54. DOI: 10.1074/jbc.M404319200. View

Ishikawa D, Yamamoto H, Tamura Y, Moritoh K, Endo T . Two novel proteins in the mitochondrial outer membrane mediate beta-barrel protein assembly. J Cell Biol. 2004; 166(5):621-7. PMC: 2172422. DOI: 10.1083/jcb.200405138. View

Chacinska A, Pfannschmidt S, Wiedemann N, Kozjak V, Sanjuan Szklarz L, Schulze-Specking A . Essential role of Mia40 in import and assembly of mitochondrial intermembrane space proteins. EMBO J. 2004; 23(19):3735-46. PMC: 522791. DOI: 10.1038/sj.emboj.7600389. View

Curran S, Leuenberger D, Leverich E, Hwang D, Beverly K, Koehler C . The role of Hot13p and redox chemistry in the mitochondrial TIM22 import pathway. J Biol Chem. 2004; 279(42):43744-51. DOI: 10.1074/jbc.M404878200. View

Naoe M, Ohwa Y, Ishikawa D, Ohshima C, Nishikawa S, Yamamoto H . Identification of Tim40 that mediates protein sorting to the mitochondrial intermembrane space. J Biol Chem. 2004; 279(46):47815-21. DOI: 10.1074/jbc.M410272200. View

Dimmer K, Jakobs S, Vogel F, Altmann K, Westermann B . Mdm31 and Mdm32 are inner membrane proteins required for maintenance of mitochondrial shape and stability of mitochondrial DNA nucleoids in yeast. J Cell Biol. 2005; 168(1):103-15. PMC: 2171677. DOI: 10.1083/jcb.200410030. View

Chacinska A, Lind M, Frazier A, Dudek J, Meisinger C, Geissler A . Mitochondrial presequence translocase: switching between TOM tethering and motor recruitment involves Tim21 and Tim17. Cell. 2005; 120(6):817-29. DOI: 10.1016/j.cell.2005.01.011. View

Mesecke N, Terziyska N, Kozany C, Baumann F, Neupert W, Hell K . A disulfide relay system in the intermembrane space of mitochondria that mediates protein import. Cell. 2005; 121(7):1059-69. DOI: 10.1016/j.cell.2005.04.011. View

10.

van der Laan M, Chacinska A, Lind M, Perschil I, Sickmann A, Meyer H . Pam17 is required for architecture and translocation activity of the mitochondrial protein import motor. Mol Cell Biol. 2005; 25(17):7449-58. PMC: 1190294. DOI: 10.1128/MCB.25.17.7449-7458.2005. View

11.

DSilva P, Schilke B, Walter W, Craig E . Role of Pam16's degenerate J domain in protein import across the mitochondrial inner membrane. Proc Natl Acad Sci U S A. 2005; 102(35):12419-24. PMC: 1194952. DOI: 10.1073/pnas.0505969102. View

12.

Rissler M, Wiedemann N, Pfannschmidt S, Gabriel K, Guiard B, Pfanner N . The essential mitochondrial protein Erv1 cooperates with Mia40 in biogenesis of intermembrane space proteins. J Mol Biol. 2005; 353(3):485-92. DOI: 10.1016/j.jmb.2005.08.051. View

13.

Allen S, Balabanidou V, Sideris D, Lisowsky T, Tokatlidis K . Erv1 mediates the Mia40-dependent protein import pathway and provides a functional link to the respiratory chain by shuttling electrons to cytochrome c. J Mol Biol. 2005; 353(5):937-44. DOI: 10.1016/j.jmb.2005.08.049. View

14.

Becker L, Bannwarth M, Meisinger C, Hill K, Model K, Krimmer T . Preprotein translocase of the outer mitochondrial membrane: reconstituted Tom40 forms a characteristic TOM pore. J Mol Biol. 2005; 353(5):1011-20. DOI: 10.1016/j.jmb.2005.09.019. View

15.

Schleiff E, Soll J . Membrane protein insertion: mixing eukaryotic and prokaryotic concepts. EMBO Rep. 2005; 6(11):1023-7. PMC: 1371041. DOI: 10.1038/sj.embor.7400563. View

16.

Sato T, Esaki M, Fernandez J, Endo T . Comparison of the protein-unfolding pathways between mitochondrial protein import and atomic-force microscopy measurements. Proc Natl Acad Sci U S A. 2005; 102(50):17999-8004. PMC: 1312372. DOI: 10.1073/pnas.0504495102. View

17.

Webb C, Gorman M, Lazarou M, Ryan M, Gulbis J . Crystal structure of the mitochondrial chaperone TIM9.10 reveals a six-bladed alpha-propeller. Mol Cell. 2006; 21(1):123-33. DOI: 10.1016/j.molcel.2005.11.010. View

18.

Meinecke M, Wagner R, Kovermann P, Guiard B, Mick D, Hutu D . Tim50 maintains the permeability barrier of the mitochondrial inner membrane. Science. 2006; 312(5779):1523-6. DOI: 10.1126/science.1127628. View

19.

Reinders J, Zahedi R, Pfanner N, Meisinger C, Sickmann A . Toward the complete yeast mitochondrial proteome: multidimensional separation techniques for mitochondrial proteomics. J Proteome Res. 2006; 5(7):1543-54. DOI: 10.1021/pr050477f. View

20.

Mokranjac D, Bourenkov G, Hell K, Neupert W, Groll M . Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor. EMBO J. 2006; 25(19):4675-85. PMC: 1590002. DOI: 10.1038/sj.emboj.7601334. View