title: Phosphatidylserine decarboxylase 1 autocatalysis and function does not require a mitochondrial-specific factor.
abstract: Phosphatidylethanolamine (PE) is a major cellular phospholipid that can be made by four separate pathways, one of which resides in the mitochondrion. The mitochondrial enzyme that generates PE is phosphatidylserine decarboxylase 1 (Psd1p). The pool of PE produced by Psd1p, which cannot be compensated for by the other cellular PE metabolic pathways, is important for numerous mitochondrial functions, including oxidative phosphorylation and mitochondrial dynamics and morphology, and is essential for murine development. To become catalytically active, Psd1p undergoes an autocatalytic processing step involving a conserved LGST motif that separates the enzyme into α and β subunits that remain non-covalently attached and are anchored to the inner membrane by virtue of the membrane-embedded β subunit. It was speculated that Psd1p autocatalysis requires a mitochondrial-specific factor and that for Psd1p to function in vivo, it had to be embedded with the correct topology in the mitochondrial inner membrane. However, the identity of the mitochondrial factor required for Psd1p autocatalysis has not been identified. With the goal of defining molecular requirements for Psd1p autocatalysis, we demonstrate that: 1) despite the conservation of the LGST motif from bacteria to humans, only the serine residue is absolutely required for Psd1p autocatalysis and function; 2) yeast Psd1p does not require its substrate phosphatidylserine for autocatalysis; and 3) contrary to a prior report, yeast Psd1p autocatalysis does not require mitochondrial-specific phospholipids, proteins, or co-factors, because Psd1p re-directed to the secretory pathway undergoes autocatalysis normally and is fully functional in vivo.
authors.affiliation: From the Department of Physiology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205.
authors.forename: Ouma
authors.initials: O
authors.lastname: Onguka
authors.affiliation: From the Department of Physiology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Calzada
authors.affiliation: From the Department of Physiology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205.
authors.forename: Oluwaseun B
authors.initials: OB
authors.lastname: Ogunbona
authors.affiliation: From the Department of Physiology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205 sclaypo1@jhmi.edu.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Claypool
mesh_terms: D020816:Amino Acid Motifs; D002262:Carboxy-Lyases / Q000235:genetics / Q000378:metabolism*; D002384:Catalysis; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics
chemical_list: D024101:Mitochondrial Proteins; D002262:Carboxy-Lyases; C577156:Psd1 protein, S cerevisiae
keywords: autocatalysis; membrane; membrane biogenesis; mitochondria; phosphatidylethanolamine; phospholipid; yeast
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