Reactome | Protein localization

Protein localization

Stable Identifier

R-HSA-9609507

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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Protein localization (Homo sapiens)

General

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Protein localization encompasses the processes that establish and maintain proteins at specific locations. Mechanisms that target proteins to particular locations in the cell typically involve a motif in the targeted protein that interacts with proteins located at the destination (reviewed in Bauer et al. 2015).
Mitochondrial proteins encoded in the nucleus may be targeted to the outer membrane, intermembrane space, inner membrane, or the matrix (reviewed in Kutik et al. 2007, Milenkovic et al. 2007, Bolender et al. 2008, Ender and Yamano 2009, Wiedemann and Pfanner 2017, Kang et al. 2018). A presequence or an internal targeting sequence causes a protein in the cytosol to interact with the TOMM40:TOMM70 complex in the outer mitochondrial membrane. After passage across the outer membrane, sequence motifs cause proteins to be targeted to the outer membrane via the SAMM50 complex, to the inner membrane via the TIMM22 or TIMM23 complexes, to the matrix via the TIMM23 complex, or proteins may fold and remain in the intermembrane space.
All of the proteins contained in the peroxisomal matrix are imported from the cytosol by a unique mechanism that does not require the imported proteins to be unfolded as they cross the membrane (reviewed in Ma et al. 2011, Fujiki et al. 2014, Francisco et al. 2017). In the cytosol, receptor proteins, PEX5 and PEX7, bind to specific sequence motifs in cargo proteins and then interact with a protein complex containing PEX13, PEX14, PEX2, PEX10, and PEX12 in the peroxisome membrane. The cargo proteins then pass through a proteinaceous channel in the membrane and PEX5 is recycled by a mechanism involving ubiquitination and deubiquitination.
Most peroxisomal membrane proteins (PMPs) are inserted into the peroxisomal membrane by the receptor-chaperone PEX19 and the docking receptor PEX3 (reviewed in Ma et al. 2011, Fujiki et al. 2014). PEX19 binds the PMP as it is translated in the cytosol. The PEX19:PMP complex then interacts with PEX3 located in the peroxisomal membrane. Through a mechanism that is not yet clear, the PMP is inserted into the peroxisomal membrane and PEX19 dissociates from PEX3.

Literature References

PubMed ID	Title	Journal	Year
17696772	Diverse mechanisms and machineries for import of mitochondrial proteins Milenkovic, D, Müller, J, Stojanovski, D, Pfanner, N, Chacinska, A	Biol Chem	2007
17998403	Cooperation of translocase complexes in mitochondrial protein import Kutik, S, Guiard, B, Meyer, HE, Wiedemann, N, Pfanner, N	J Cell Biol	2007
19453276	Multiple pathways for mitochondrial protein traffic Endo, T, Yamano, K	Biol Chem	2009
18174896	Multiple pathways for sorting mitochondrial precursor proteins Bolender, N, Sickmann, A, Wagner, R, Meisinger, C, Pfanner, N	EMBO Rep	2008
28301740	Mitochondrial Machineries for Protein Import and Assembly Wiedemann, N, Pfanner, N	Annu. Rev. Biochem.	2017
28765093	Mitochondrial protein transport in health and disease Kang, Y, Fielden, LF, Stojanovski, D	Semin. Cell Dev. Biol.	2018
25177298	Peroxisome biogenesis in mammalian cells Fujiki, Y, Okumoto, K, Mukai, S, Honsho, M, Tamura, S	Front Physiol	2014
28787099	Protein transport into peroxisomes: Knowns and unknowns Francisco, T, Rodrigues, TA, Dias, AF, Barros-Barbosa, A, Bicho, D, Azevedo, JE	Bioessays	2017
26172624	Mechanisms Regulating Protein Localization Bauer, NC, Doetsch, PW, Corbett, AH	Traffic	2015
21464226	Peroxisome assembly: matrix and membrane protein biogenesis Ma, C, Agrawal, G, Subramani, S	J. Cell Biol.	2011