アクティブボード・２０１２年　２月
　　　　　・・・・・２０１２年　２月　２日更新・・・・・

研究発表を行った学会；
・第３４回　日本分子生物学会年会
　２０１１年１２月１３日〜１６日（横浜）

タイトル；A cytosolic AAA chaperone Cdc48p/p97 regulates mitochondrial morphology.

発表者；江崎　雅俊　氏
　　　（熊本大学　発生医学研究所　分子細胞制御分野）
Abstract；
Cdc48p, also known as p97 and VCP, is an essential AAA protein and is highly conserved among species. Cdc48p is well known to participate in various cellular processes including ER-associated protein degradation, reorganization of the Golgi complex, and cell cycle control. We recently found that yeast Cdc48p is involved in the maintenance of mitochondrial morphology.
Cdc48p is composed of two AAA ATPase domains (D1 and D2), which form a tandem ring-shaped hexamer. We have found that ATPase-deficient mutations in D1 is viable and does not lead to severe morphological defects of intracellular organelles such as mitochondria, ER, and the Golgi complex. In contrast, ATPase activity of D2, especially its positive cooperativity, is essential for cell viability. Loss of the positive cooperativity leads to severe morphological alteration in the Golgi complex, suggesting that the membrane fusion of Golgi cisternae requires the positively cooperative ATPase activity of Cdc48p. To our surprise, mitochondrial morphology is also significantly affected by the loss of the positive cooperativity. Turnovers of some mitochondrial outer membrane proteins involved in mitochondrial dynamics are delayed in the cdc48 mutant cells. Recently, Vms1 has been identified as a cofactor of Cdc48p for degradation of mitochondrial outer membrane proteins. However,
abnormal mitochondrial morphology and the delayed protein turnovers are still observed in the vms1 deletion strains. These results suggest that Cdc48p, together with unidentified cofactor(s), is involved in the maintenance of mitochondrial morphology by regulating protein turnover on the mitochondrial outer membrane.