ABERRANT MITOCHONDRIA RESPIRATION IN THE LIVERS OF RATS INFECTED WITHFASCIOLA-HEPATICA - THE ROLE OF ELEVATED NONESTERIFIED FATTY-ACIDS AND ALTERED PHOSPHOLIPID-COMPOSITION

The non-esterified fatty acid (NEFA) content and phospholipid composit ion of mitochondria isolated from the livers of Wistar rats infected w ith Fasciola hepatica were examined in relation to the aberrant mitoch ondrial respiration previously reported [Rule, Behm, and Bygrave (1989 ) Biochem. J. 260, 517-523]. At 2 weeks post-infection, elevated NEFA levels were associated with uncoupling of mitochondrial respiration th at was reversible in vitro by the addition of BSA, State IV respiratio n rates showed a strong correlation with NEFA content, At 3 weeks post -infection, NEFA content had increased further and uncoupled mitochond ria no longer showed any response to BSA, P-31-NMR analyses of cholate extracts of mitochondria from infected livers at 3 weeks post-infecti on revealed a marked loss of several major phospholipid species with a concomitant increase in catabolic products, particularly glycerophosp hocholine and glycerophosphoethanolamine. Similar changes were observe d in microsomal extracts. The NEFA content and phospholipid compositio n of mitochondria isolated from infected, athymic nude rats were not s ignificantly different from uninfected, athymic rats. These findings s uggest that uncoupling of liver mitochondria during infection with F. hepatica is the result of phospholipase activation mediated by the imm une system of the host.