Agmatine is transported in liver mitochondria by a specific electrophoretic mechanism

• Published in: Biochemical journal Vol. 396; no. 2; pp. 337 - 345
• Main Authors: Salvi, Mauro, Battaglia, Valentina, Mancon, Mario, Colombatto, Sebastiano, Cravanzola, Carlo, Calheiros, Rita, Marques, Maria Mp, Grillo, Maria A, Toninello, Antonio
• Format: Journal Article
• Language: English
• Published: Portland Press 02.03.2006
• Subjects: Life Sciences
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/BJ20060003

Agmatine, a divalent diamine having two positive charges at physiological pH, is transported into the matrix of liver mitochondria by an energy-dependent mechanism whose driving force is the electrical membrane potential ({Delta}{Psi}). Although this process shows strict electrophoretic behavior, qualitatively similar to that of polyamines, agmatine is most probably transported by a specific uniporter. Common transport with polyamines, by means of their transporter, must be excluded, as the divalent putrescine and cadaverine are ineffective in inhibiting agmatine uptake. Indeed, use of the electroneutral transporter of basic amino acids is also to be discarded, as ornithine, arginine and lysine are completely ineffective in inducing inhibition of agmatine uptake. Involvement of the monoamine transporter or the existence of a leak pathway are also unlikely. Flux-voltage analysis and determination of activation enthalpy, depending on the valence of agmatine, are consistent with the hypothesis that the mitochondrial agmatine transporter is a channel or a single-binding center-gated pore. The transport of agmatine is non-competitively inhibited by propargylamines, in particular clorgilyne, known to be inhibitors of monoamine oxidase (MAO). However, agmatine is normally transported in mitoplasts, thus excluding the involvement of MAO in this process. The I2 imidazoline receptor, which binds agmatine to the mitochondrial membrane, must also be excluded as a possible transporter since its inhibitor, idazoxan, is ineffective in inducing inhibition of agmatine uptake. Scatchard analysis of membrane binding revealed two types of binding sites, S1 and S2, both with monocoordination and exhibiting high capacity and low affinity compared with polyamines. Agmatine transport in liver mitochondria may be of physiological importance as an indirect regulatory system of cytochrome c oxidase activity and an inducer mechanism of mitochondrial-mediated apoptosis.