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 mitochondria 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 ratio also reached a peak value 48 hours after hepatectomy. No significant change was found in state 4 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 chloramphenicol-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 corresponds well to this energy demand, suggesting it may play an important role in the process of liver regeneration.