Abstract

The mitochondrial carnitine/acylcarnitine transporter (CACT) catalyses carnitine/acylcarnitine antiport. Its function has been defined mainly in proteoliposome experimental models. Despite CACT represents a putative site of?-oxidation regulation, few data are available about its modulation.Lysineacetylationisapost-translationalmodification(PTM) of a huge number of proteins. It has been shown that iper-acetylation of longchainacylCoAdehydrogenase(LCAD)impairsitsenzymaticactivity. It could be hypothesized that other components of the same pathway, suchasCACT,couldberegulatedbyasimilarmechanism.Indeed,CACTis partially acetylated in rat liver as revealed by WB analysis using an antiacetyl-Lys antibody. Acetylation can be reversed by the mitochondrial deacetylase SIRT3. After treatment of the mitochondrial extract with SIRT3, the CACT activity, assayed in proteoliposomes, increases with respect to the untreated control. The half-saturation constant is not influenced, while the Vmax is increased. The kinetic data suggests that steric hindrance of acetyl groups impairs conformational changes, rather than substrate binding. Recently, it was shown that acetylation of mitochondrial proteins also occur by a non-enzymatic pathway under conditionsofreducedAcetyl-CoAbuffering[1].RecombinantCACTwhich is not acetylated was incubated with acetyl-CoA and then subjected to WB withanti-acetyl-Lys antibodyand transportassay. Datashowed that non-enzymatic acetylation of CACT occurs and impairs its activity. In conclusion,CACTisregulatedbyacetylationrepresentingacontrolsiteof beta-oxidation pathway togetherwith LCAD.

Autore Pugliese

• Tonazzi Annamaria , Giangregorio Nicola

Tutti gli autori

• L. Console; N. Giangregorio; A. Tonazzi; C. Indiveri

Titolo volume/Rivista

Biochimica et biophysica acta. Bioenergetics

Anno di pubblicazione

2016

ISSN

0005-2728

ISBN

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Numero di citazioni Wos

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Numero di citazioni Scopus

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Settori ERC

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Codici ASJC

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