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Common ground for protein translocation: access control for mitochondria and chloroplasts

Key Points

  • The vast majority of mitochondrial and chloroplast proteins are cytosolically synthesized and have to be translocated into the organelle.

  • Precursor proteins contain amino acid-based signals. These signals supply information allowing the proteins to target, and interact with, the cytosolic chaperones that provide guidance to organelles.

  • Translocases at the outer membrane of mitochondria and chloroplasts form the general entry gate into both organelles.

  • The translocases of both organelles consist of three receptors, which bind to the multitude of different precursor proteins and deliver them to a translocation pore formed by a protein with β-barrel structure.

  • Despite similarities with respect to their composition, the translocons differ with respect to signal length requirement and their energizing of the translocation event.

  • The mode of translocation is also distinct between the translocation machineries: mitochondrial import across the outer membrane is affinity-driven, whereas the passage of precursor proteins into chloroplasts is modulated by GTP binding and hydrolysis, and by phosphorylation events.

Abstract

Mitochondria and chloroplasts import the vast majority of their proteins across two membranes, and use translocases of the outer membrane as an entry gate. These translocases interact with the incoming precursor protein and guiding chaperone factors. Within the translocon, precursor-protein receptors dock to a central component that mediates both transfer through a cation-selective channel and initial sorting towards internal subcompartments. Despite these similarities, the mode of translocation differs between the two organelles: in chloroplasts, GTP-binding and hydrolysis by the receptors is required for transport, whereas in mitochondria passage of the preprotein is driven by its increasing affinity for the translocase subunits.

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Figure 1: Protein transport into mitochondria and chloroplasts.
Figure 2: Transport of precursor proteins from the cell cytosol into mitochondria and chloroplasts.
Figure 3: The translocon of the outer membrane of mitochondria and chloroplasts.
Figure 4: Signal length requirement and translocon initiation.

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Acknowledgements

T.B. thanks N. Pfanner for support. The work was supported by Baden-Württemberg Stiftung (T.B.), the Deutsche Forschungsgemeinschaft (DFG) in the frame of the Sonderforschungsbereich SFB746 (T.B.), the Volkswagen-foundation (E.S.) and the DFG in the frame of the Sonderforschungsbereich SFB807/P17 (E.S.).

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Glossary

Endosymbiosis

Endosymbiosis is the process in which a free-living bacteria — the ancestral endosymbiont — was enclosed by a cell and, during evolution, became integrated into the cellular network. By transfer of most of its genetic content to the host, the nucleus lost its independence and became an organelle.

Thylakoid membrane

A component of chloroplasts, the thylakoid membrane is a specialized membranous compartment where photosynthesis occurs.

Oxygenic photosynthesis

Oxygenic photosynthesis is the conversion of carbon dioxide and water into organic compounds, especially sugars, and oxygen by the thylakoid and stromal enzymes, including the photosystems.

Amphiphilic α-helix

An amphiphilic α-helix is a helix in which one side is composed of hydrophobic amino acids and the other of hydrophilic amino acids.

β-barrel proteins

β-barrel proteins are membrane proteins that are typically found in the outer membrane of mitochondria, of chloroplasts and of Gram-negative bacteria. These proteins form a membrane-inserted barrel composed of β-strands.

14-3-3 proteins

Proteins that are expressed in eukaryotic cells and that bind preferentially to phosphorylated regions in diverse proteins involved in signal transduction and protein translocation.

Tetratricopeptide repeat

(TPR). A structural motif, found in a wide variety of proteins, that is composed of 34 amino acids. TPRs are involved in intra- and inter-molecular interactions.

Ankyrin

Ankyrin repeats are structurally but not functionally conserved units of 33 amino acids that consist of two α-helices separated by a loop, and comprise one of the most common structural motifs identified in bacterial, archaeal and eukaryotic proteins.

ERMES complex

(Endoplasmic reticulummitochondria encounter structure complex). This is the complex that tethers mitochondria and the endoplasmic reticulum. It is composed of the two mitochondrial membrane proteins Mdm34 and Mdm10, the integral endoplasmic reticulum membrane protein Mmm1 and the peripheral protein Mdm12.

Chemical crosslinking

Chemical crosslinking is the introduction of synthetic bonds that link two proteins in close proximity by chemical molecules — for example, by maleimide, which reacts with the thiol group of cysteines.

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Schleiff, E., Becker, T. Common ground for protein translocation: access control for mitochondria and chloroplasts. Nat Rev Mol Cell Biol 12, 48–59 (2011). https://doi.org/10.1038/nrm3027

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