Citrate release by perfused rat hearts: a window on mitochondrial cataplerosis

Citation
G. Vincent et al., Citrate release by perfused rat hearts: a window on mitochondrial cataplerosis, AM J P-ENDO, 278(5), 2000, pp. E846-E856
Citations number
35
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
ISSN journal
01931849 → ACNP
Volume
278
Issue
5
Year of publication
2000
Pages
E846 - E856
Database
ISI
SICI code
0193-1849(200005)278:5<E846:CRBPRH>2.0.ZU;2-L
Abstract
Cytosolic citrate is proposed to play a crucial role in substrate fuel sele ction in the heart. However, little is known about factors regulating the t ransfer of citrate from the mitochondria, where it is synthesized, to the c ytosol. Further to our observation that rat hearts perfused under normoxia release citrate whose C-13 labeling pattern reflects that of mitochondrial citrate (B. Comte, G. Vincent, B. Bouchard, and C. Des Rosiers. J. Biol. Ch em. 272: 26117-26124, 1997), we report here data indicating that this citra te release is a specific process reflecting the mitochondrial efflux of cit rate, a process referred to as cataplerosis. Indeed, measured rates of citr ate release, which vary between 2 and 21 nmol/min, are modulated by the nat ure and concentration of exogenous substrates feeding acetyl-CoA (fatty aci d) and oxaloacetate (lactate plus pyruvate) for the mitochondrial citrate s ynthase reaction. Such release rates that represent at most 2% of the citri c acid cycle flux are in agreement with the activity of the mitochondrial t ricarboxylate transporter whose participation is also substantiated by I) p arallel variations in citrate release rates and tissue levels of citrate pl us malate, the antiporter, and 2) a lowering of the citrate release rate by 1,2,3-benzenetricarboxylic acid, a specific inhibitor of the transporter. Taken together, the results from the present study indicate that citrate ca taplerosis is modulated by substrate supply, in agreement with the role of cytosolic citrate in fuel partitioning, and occurs, at least in part, throu gh the mitochondrial tricarboxylate transporter.