title: APOOL is a cardiolipin-binding constituent of the Mitofilin/MINOS protein complex determining cristae morphology in mammalian mitochondria.
abstract: Mitochondrial cristae morphology is highly variable and altered under numerous pathological conditions. The protein complexes involved are largely unknown or only insufficiently characterized. Using complexome profiling we identified apolipoprotein O (APOO) and apolipoprotein O-like protein (APOOL) as putative components of the Mitofilin/MINOS protein complex which was recently implicated in determining cristae morphology. We show that APOOL is a mitochondrial membrane protein facing the intermembrane space. It specifically binds to cardiolipin in vitro but not to the precursor lipid phosphatidylglycerol. Overexpression of APOOL led to fragmentation of mitochondria, a reduced basal oxygen consumption rate, and altered cristae morphology. Downregulation of APOOL impaired mitochondrial respiration and caused major alterations in cristae morphology. We further show that APOOL physically interacts with several subunits of the MINOS complex, namely Mitofilin, MINOS1, and SAMM50. We conclude that APOOL is a cardiolipin-binding component of the Mitofilin/MINOS protein complex determining cristae morphology in mammalian mitochondria. Our findings further assign an intracellular role to a member of the apolipoprotein family in mammals.
authors.affiliation: Mitochondrial Biology, Buchmann Institute for Molecular Life Sciences, Goethe University, Frankfurt am Main, Germany.
authors.forename: Tobias A
authors.initials: TA
authors.lastname: Weber
authors.forename: Sebastian
authors.initials: S
authors.lastname: Koob
authors.forename: Heinrich
authors.initials: H
authors.lastname: Heide
authors.forename: Ilka
authors.initials: I
authors.lastname: Wittig
authors.forename: Brian
authors.initials: B
authors.lastname: Head
authors.forename: Alexander
authors.initials: A
authors.lastname: van der Bliek
authors.forename: Ulrich
authors.initials: U
authors.lastname: Brandt
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
authors.forename: Andreas S
authors.initials: AS
authors.lastname: Reichert
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000378:metabolism*; D002308:Cardiolipins / Q000378:metabolism*; D002417:Cattle; D015536:Down-Regulation; D006367:HeLa Cells; D006801:Humans; D008322:Mammals / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D008929:Mitochondria, Heart / Q000378:metabolism / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000378:metabolism / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D010101:Oxygen Consumption; D011485:Protein Binding
chemical_list: C585262:APOOL protein, human; D001053:Apolipoproteins; D002308:Cardiolipins; C088548:IMMT protein, human; C573118:MINOS1 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D046912:Multiprotein Complexes; D009124:Muscle Proteins