Mitochondrial calcium ion and oxidative phosphorylation in regenerating rat liver

Background and Purpose: Liver regeneration develops after partial hepatectomy. This study investigated the enhancement of oxidative phosphorylation in liver regeneration and its correlation to mitochondrial calcium ion in rats. Methods: Respiratory functions of mitochondrial isolated from regenerating rat liver 24, 48, 72 and 96 hours after 70% hepatectomy were studied including state 3 and state 4 oxygen consumption, respiratory control (RC) ratio, and ADP/O (molecules of adenosine diphosphate production per molecule of oxygen). Intramitochondrial matrix free calcium ion concentration ([Ca2+](m)) was measured using the fluo-3 loading method. The changes in state 3 oxygen consumption and [Ca2+] were also evaluated in chloramphenicol-treated mitochondria, which were isolated from rats subjected to chloramphenicol injection for 48 hours. Results: State 3 oxygen consumption was significantly enhanced 48 hours post-hepatectomy. The RC ration also reached a peak value 48 hours after hepatectomy. No significant change was found in state 1 oxygen consumption and ADP/O during the first 96 hours after hepatectomy. The [Ca2+](m) was significantly elevated as early as 24 hours post-hepatectomy, and reached its peak value 48 hours post-hepatectomy. The mitochondrial total calcium concentration was also elevated at 24 hours post-hepatectomy, but returned to near the control level 48 hours post-hepatectomy. In the chloroamphenicol-treated group, state 3 oxygen consumption was depressed at 48 hours compared to the post-hepatectomy group, while the [Ca2+](m) was significantly increased. Conclusions: The energy demand for liver regeneration is enhanced after partial hepatectomy, [Ca2+](m) correspond well to this energy demand, suggesting it may play an important role in the process of liver regeneration.