Editing Protein targeting (section)

==== Mitochondrial intermembrane space ====
If instead the precursor protein is designated to the intermembrane space of the mitochondrion, there are two pathways this may occur depending on the sequences being recognized. The first pathway to the intermembrane space follows the same steps for an inner membrane targeted protein. However, once bound to the inner membrane the [[C-terminus]] of the anchored protein is cleaved via a peptidase that liberates the preprotein into the intermembrane space so it can fold into its active state.<ref name="Lodish, Berk, Kaiser, Krieger, Bretscher, Ploegh, Martin, Yaffe, Amon-2021" /><ref name="Wiedemann N, Pfanner N-2017" /> One of the greatest examples for a protein that follows this pathway is [[Cytochrome b|cytochrome b2]], that upon being cleaved will interact with a [[heme]] cofactor and become active.<ref name="Lodish, Berk, Kaiser, Krieger, Bretscher, Ploegh, Martin, Yaffe, Amon-2021" /><ref>{{Cite journal |last=Shwarz E, Seytter T, Guiard B, Neupert W |date=1993 |title=Targeting of cytochrome b2 into the mitochondrial intermembrane space: specific recognition of the sorting signal. |journal=EMBO J |volume=12 |via=PubMed}}</ref> The second intermembrane space pathway does not utilize any inner membrane complexes and therefor does not contain a matrix targeting signal. Instead, it enters through the general import core TOM40 and is further modified in the intermembrane space to achieve its active conformation. TIM9/10 is an example of a protein that follows this pathway in order to be in the location it needs to be to assist in inner membrane targeting.<ref name="Lodish, Berk, Kaiser, Krieger, Bretscher, Ploegh, Martin, Yaffe, Amon-2021" /><ref name="Wiedemann N, Pfanner N-2017" /><ref>{{Cite journal |last=Kurz M, Martin H, Rassow J, Pfanner N, Ryan M |date=2017 |title=Biogenesis of Tim Proteins of the Mitochondrial Carrier Import Pathway: Differential Targeting Mechanisms and Crossing Over with the Main Import Pathway |journal=Molecular Biology of the Cell |volume=10 |issue=7 |pages=2461–2474 |doi=10.1091/mbc.10.7.2461 |pmid=10397776 |pmc=25469 }}</ref>