| 研究実績の概要 |
I have identified several downstream genes of HKII using chromatin immunoprecipitation (ChIP) and validated their actions in HKII mediated autophagy. Using both in vitro and in vivo analysis, I found that mTOR is antagonized by HKII while AMPK and ULK are directly activated by HKII. Importantly we found that, starvation induces HKII-AMPK-ULK pathway while steroid manipulation or temperature stress bypasses the AMPK action and shifts them to HKII-ULK pathway. We also determined that HKII pathway is accelerated during early stages of E.tarda infection, but not from irridoviral infection. To understand better, we isolated the mitochondria from female and male red sea bream liver hepatocytes, subjected it to various stressors (starvation, high temperature and steroid manipulation) and infections, and found a clear sex specific differences in mitochondria HKII expression in all the samples except for the irridovirus infected hepatocytes. Notably, all these events reduces the glucose content in mitochondria. Our data suggests that, HKII, a glycolytic molecule, can sense mitochondrial glucose derangements, and modulate its intracellular localization and thus can regulate mitophagy and cellular autophagy in fish.
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