title: CoA synthase is in complex with p85alphaPI3K and affects PI3K signaling pathway.
abstract: The complex interplay between cellular signaling and metabolism in eukaryotic cells just start to emerge. Coenzyme A (CoA) and its derivatives play a key role in cell metabolism and also participate in regulatory processes. CoA synthase (CoASy) is a mitochondria-associated enzyme which mediates two final stages of de novo CoA biosynthesis. Here, we report that CoASy is involved in signaling events in the cell and forms a functional complex with p85alphaPI3K in vivo. Importantly, observed interaction of endogenous CoASy and p85alphaPI3K is regulated in a growth factor dependent manner. Surprisingly, both catalytic p110alpha and regulatory p85alpha subunits of PI3K were detected in mitochondrial fraction where mitochondria-localized p85alphaPI3K was found in complex with CoASy. Unexpectedly, significant changes of PI3K signaling pathway activity were observed in experiments with siRNA-mediated CoASy knockdown pointing on the role of CoA biosynthetic pathway in signal transduction.
authors.affiliation: Department of Cell Signalling, Institute of Molecular Biology and Genetics National Academy of Sciences of Ukraine, Kyiv, Ukraine.
authors.forename: Oksana
authors.initials: O
authors.lastname: Breus
authors.forename: Ganna
authors.initials: G
authors.lastname: Panasyuk
authors.forename: Ivan T
authors.initials: IT
authors.lastname: Gout
authors.forename: Valeriy
authors.initials: V
authors.lastname: Filonenko
authors.forename: Ivan
authors.initials: I
authors.lastname: Nemazanyy
mesh_terms: D002460:Cell Line; D055785:Gene Knockdown Techniques; D006801:Humans; D047468:Immunoprecipitation; D008928:Mitochondria / Q000201:enzymology; D009097:Multienzyme Complexes / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D014166:Transferases / Q000235:genetics / Q000378:metabolism*; D018909:src Homology Domains
chemical_list: D009097:Multienzyme Complexes; D034741:RNA, Small Interfering; D014166:Transferases; D019869:Phosphatidylinositol 3-Kinases; C509687:COASY protein, human