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Protein targeting
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==== Mitochondrial inner membrane ==== Targeting of mitochondrial proteins to the inner membrane may follow 3 different pathways depending upon their overall sequences, however, entry from the outer membrane remains the same using the import receptor complex TOM20/22 and TOM40 general import core.<ref name="Lodish, Berk, Kaiser, Krieger, Bretscher, Ploegh, Martin, Yaffe, Amon-2021" /><ref name="Eaglesfield R, Tokatlidis K-2021" /> The first pathway for proteins targeted to the inner membrane follows the same steps as those designated to the matrix where it contains a matrix targeting sequence that channels the polypeptide to the inner membrane complex containing the previously mentioned translocase complex TIM17/23/44.<ref name="Lodish, Berk, Kaiser, Krieger, Bretscher, Ploegh, Martin, Yaffe, Amon-2021" /><ref name="Eaglesfield R, Tokatlidis K-2021" /><ref name="Wiedemann N, Pfanner N-2017" /> However, the difference is that the peptides that are designated to the inner membrane and not the matrix contain an upstream sequence called the stop-transfer-anchor sequence.<ref name="Lodish, Berk, Kaiser, Krieger, Bretscher, Ploegh, Martin, Yaffe, Amon-2021" /> This stop-transfer-anchor sequence is a hydrophobic region that embeds itself into the [[Lipid bilayer|phospholipid bilayer]] of the inner membrane and prevents translocation further into the mitochondrion.<ref name="Eaglesfield R, Tokatlidis K-2021" /><ref name="Wiedemann N, Pfanner N-2017" /> The second pathway for proteins targeted to the inner membrane follows the matrix localization pathway in its entirety. However, instead of a stop-transfer-anchor sequence, it contains another sequence that interacts with an inner membrane protein called Oxa-1 once inside the matrix that will embed it into the inner membrane.<ref name="Lodish, Berk, Kaiser, Krieger, Bretscher, Ploegh, Martin, Yaffe, Amon-2021" /><ref name="Eaglesfield R, Tokatlidis K-2021" /><ref name="Wiedemann N, Pfanner N-2017" /> The third pathway for mitochondrial proteins targeted to the inner membrane follow the same entry as the others into the outer membrane, however, this pathway utilizes the translocase complex TIM22/54 assisted by complex TIM9/10 in the intermembrane space to anchor the incoming peptide into the membrane.<ref name="Lodish, Berk, Kaiser, Krieger, Bretscher, Ploegh, Martin, Yaffe, Amon-2021" /><ref name="Eaglesfield R, Tokatlidis K-2021" /><ref name="Wiedemann N, Pfanner N-2017" /> The peptides for this last pathway do not contain a matrix targeting sequence, but instead contain several internal targeting sequences.
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