INVESTIGADORES
CORVI Maria Martha
artículos
Título:
Identification of palmitoylated mitochondrial proteins using a bio-orthogonal azido-palmitate analogue
Autor/es:
CORVI MM; KOSTIUK MA; KELLER BO; PLUMMER G; PRESCHER JA; HANGAUER MJ; BERTOZZI CR; RAJAIAH G; FALCK JR; BERTHIAUME LG
Revista:
FASEB JOURNAL
Editorial:
FEDERATION AMER SOC EXP BIOL
Referencias:
Año: 2008 vol. 22 p. 721 - 732
ISSN:
0892-6638
Resumen:
Increased levels of circulating saturated free fatty acids such as palmitate have been
implicated in the etiology of type II diabetes and cancer. In addition to being a constituent of
glycerolipids and a source of energy, palmitate also covalently attaches to numerous cellular
proteins via a process named palmitoylation. Recognized for its roles in membrane tethering,
cellular signaling and protein trafficking, palmitoylation is also emerging as a potential regulator
of metabolism. Indeed, we previously showed that the acylation of two mitochondrial proteins at
their active site cysteine residues resulting in their inhibition. Herein, we sought to identify other
palmitoylated proteins in mitochondria using a non-radioactive bioorthogonal azido-palmitate
analogue that can be selectively derivatized with various tagged-triarylphosphines. Our results
show that like palmitate, incorporation of azido-palmitate occurred on mitochondrial proteins via
thioester bonds at sites that could be competed by palmitoyl-CoA. Using this method, we
identified 21 palmitoylated proteins in the rat liver mitochondrial matrix, a compartment not
recognized for its content in palmitoylated proteins and confirmed the palmitoylation of newly
identified mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase. We postulate that covalent
modification and perhaps inhibition of various mitochondrial enzymes by palmitoyl-CoA could
lead to the metabolic impairments found in obesity related diseases.