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#mitochondrial inner membrane

2 public questions tagged with this topic.

Protein Sorting and Trafficking

What is the function of the OXA complex in mitochondria?

Evolutionary conservation membrane insertases bacterial plasma membrane reveals OXA family YidC Alb3 Oxa1. Mitochondrial Oxa1 45 kDa inner membrane five transmembrane helices forms co-translational insertion site adjacent matrix mitoribosome large subunit near exit tunnel via Mrpl45 interaction. Several highly hydrophobic proteins encoded mitochondrial DNA including subunit II III cytochrome oxidase Cox2 Cox3 subunit a c ATP synthase Atp6 Atp9 cytochrome b Cob synthesized matrix mitoribosomes because extreme hydrophobicity would hamper import. Oxa1 central hydrophilic groove provides aqueous path lateral gate opening lipid bilayer facilitating insertion nascent helices using positive inside rule proton motive force independent ATP. Nuclear-encoded proteins first fully imported matrix via TIM23 such Cox18 dependent and some ATP synthase subunits also require subsequent export inner membrane conservative sorting analogous Sec-independent insertion again via Oxa1. Oxa1 does not insert beta-barrel outer proteins relying SAM complex Tob55 nor directly drive matrix import via TIM23 nor act proton pump; Complexes I III IV pump protons. Deletion Oxa1 yeast pleiotropic respiratory deficiency failure assembling Complexes IV V loss membrane potential and biogenesis.

Ref: Hennon et al., Front Physiol 2015: OXA insertase inserts proteins into mitochondrial inner membrane.

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Protein Sorting and Trafficking

Which pathway is used for the import of ATP/ADP antiporter into the mitochondrial inner membrane?

Inner membrane metabolite carriers including ADP/ATP antiporter ANT1-3, phosphate carrier PiC, dicarboxylate, citrate, aspartate-glutamate belong SLC25 family tripartite three repeats each two helices total six without cleavable presequence. Internal targeting hydrophobic modules recognized post-translationally. After synthesis cytosol association Hsp70 Hsp90 chaperones cross outer TOM complex using Tom70 receptor. Intermembrane space TIM chaperone hexameric small Tim proteins Tim9-Tim10-Tim12 twin CX3C subunits cage shielding hydrophobic transmembrane segments preventing aggregation aqueous environment. For insertion they engage TIM22 translocase 300 kDa containing Tim22 twin voltage-gated pores each four helices Tim18 stabilizing Tim54 peripheral organizing Sdh3 subunit Complex II moonlighting Tim12 bridging small Tims. Membrane potential Delta psi drives hairpin-loop insertion positively charged loops electrophoresed lateral release bilayer. TIM23 pathway handles presequence matrix proteins via PAM motor, OXA inserts mitochondrially encoded hydrophobic subunits co-translationally matrix side, SAM assembles outer beta-barrels. TIM22 dedicated polytopic inner carriers essential metabolite exchange respiration regulation energy homeostasis and nucleotide transport across mitochondria.

Ref: Rehling et al., Nat Rev Mol Cell Biol 2004: TIM22 imports ADP/ATP carrier into inner membrane.

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