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Property "Has-20abstract" (as page type) with input value "-5B-5BImage:MITOEAGLE-2Dlogo.jpg-7Cleft-7C100px-7Clink=http:-2F-2Fwww.mitoglobal.org-2Findex.php-2FMITOEAGLE-7CCOST-20Action-20MITOEAGLE-5D-5D-20Mitochondrial-20F-3Csub-3E1-3C-2Fsub-3EF-3Csub-3EO-3C-2Fsub-3E-20ATP-20synthase-20is-20the-20key-20enzyme-20of-20the-20oxidative-20phosphorylation-20apparatus,-20responsible-20for-20the-20production-20of-20up-20to-2090-25-20of-20the-20cellular-20ATP.-20The-20mammalian-20enzyme-20is-20composed-20of-2017-20structural-20subunits-20–-20two-20of-20the-20recently-20characterized-20ones-20(MLQ-20and-20DAPIT)-20are-20specific-20for-20higher-20eukaryotes.-20MLQ,-20also-20termed-206.8-20kDa-20proteolipid-20(MP68),-20is-20nuclearly-20encoded-20protein-20with-2058-20amino-20acids,-20containing-20one-20putative-20membrane-20domain.-20The-20complete-20structure-20of-20MLQ,-20its-20stoichiometry-20within-20the-20enzyme,-20or-20its-20exact-20localization-20in-20the-20F-3Csub-3EO-3C-2Fsub-3E-20domain-20is-20as-20of-20yet-20unknown.-0A-0ATo-20clarify-20the-20biological-20role-20of-20MLQ,-20we-20created-20a-20MLQ-20knock-2Dout-20model-20in-20the-20HEK293-20cells-20by-20the-20CRISPR-2FCas9-20technology.-20We-20demonstrate-20defective-20biogenesis-20of-20the-20fully-20assembled-20ATP-20synthase-20in-20the-20absence-20of-20MLQ.-20While-20mitochondrially-20encoded-20subunits-20F-3Csub-3EO-3C-2Fsub-3E-2Da-20and-20A6L-20are-20synthesized-20and-20assembled-20into-20the-20complex,-20MLQ-20is-20required-20for-20their-20stabilization-20in-20the-20holoenzyme.-20In-20its-20absence,-20F-3Csub-3EO-3C-2Fsub-3E-2Da-20and-20A6L-20dissociate-20and-20are-20degraded-20as-20confirmed-20by-20pulse-20chase-20experiments.-20As-20a-20result,-20at-20the-20steady-20state,-20incomplete-20enzyme-20lacking-20the-20proton-20channel-20formed-20by-20subunit-20F-3Csub-3EO-3C-2Fsub-3E-2Da-20is-20present-20in-20MLQ-20-2D-2F-2D-20mitochondria.-20At-20the-20functional-20level,-20we-20observed-20significantly-20reduced-20rates-20of-20ADP-20stimulated-20respiration-20in-20MLQ-20-2D-2F-2D-20cells,-20while-20the-20hydrolytic-20activity-20of-20the-20ATP-20synthase-20was-20preserved.-20Secondary-20to-20the-20ATP-20synthase-20deficiency-20we-20observed-20decreased-20mRNA-20and-20protein-20levels-20of-20the-20mitochondrially-20encoded-20subunits-20of-20cytochrome-20-27-27c-27-27-20oxidase-20(CIV).-20This-20led-20to-20the-20reduced-20levels-20of-20COX-20holoenzyme-20and-20decrease-20in-20ATP-20synthase-20independent-20state-203-20(FCCP)-20respiration.-0A-0AWe-20will-20discuss-20the-20molecular-20role-20of-20MLQ-20in-20F-3Csub-3E1-3C-2Fsub-3EF-3Csub-3EO-3C-2Fsub-3E-20ATP-20synthase-20assembly-20as-20well-20as-20the-20functional-20impact-20of-20MLQ-20KO-20on-20the-20cellular-20energetics.-20Moreover,-20we-20will-20report-20on-20progress-20of-20F-3Csub-3EO-3C-2Fsub-3E-2Da-20and-20A6L-20subunits-20degradation-20mechanism-20in-20MLQ-20KO-20cells." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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