Huang Li-Ju, Hsu Chin, Tsai Tsen-Ni, Wang Shu-Jung, Yang Rei-Cheng
Department of Physiology, Graduate Institute of Medicine, Kaohsiung Medical University, and Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
Biochim Biophys Acta. 2007 Jul;1767(7):888-96. doi: 10.1016/j.bbabio.2007.03.009. Epub 2007 Apr 3.
Sepsis and ensuing multiple organ failure continue to be the most leading cause of death in critically ill patients. Despite hepatocyte-related dysfunctions such as necrosis, apoptosis as well as mitochondrial damage are observed in the process of sepsis, the molecular mechanism of pathogenesis remains uncertain. We recently identified one of the differentially expressed genes, mitochondrial ATPase inhibitor protein (IF1) which is down-regulated in late septic liver. Hence, we further hypothesized that the variation of IF1 protein may be one of the causal events of the hepatic dysfunction during late sepsis. The results showed that the elevated mitochondrial F0F1-ATPase activity is concomitant with the decline of intramitochondrial ATP concentration in late septic liver. In addition, the key finding of this study showed that the mRNA and the mitochondrial content of IF1 were decreased in late sepsis while no detectable IF1 was found in cytoplasm. When analyzed by immunoprecipitation, it seems reasonable to imply that the association capability of IF1 with F1-ATPase beta-subunit is not affected. These results confirm the first evidence showing that the suppression of IF1 expression and subsequent elevated mitochondrial F0F1-ATPase activity might contribute to the bioenergetic failure in the liver during late sepsis.
