Srv2蛋白在酵母菌粒線體的動態平衡所扮演的角色

粒線體在細胞內能進行氧化磷酸化合成ATP，同時參與許多攸關細胞存亡的訊息傳遞，因此對細胞非常重要。粒線體透過各種調控機制來進行融合、分裂及細胞內的移動不斷改變其形態，稱之粒線體動態平衡。粒線體的動態平衡與其功能調控有緊密的關聯，粒線體動態平衡失調在能量需求高的細胞中常常造成嚴重的疾病，例如：神經退化疾病及心血管疾病，顯示出粒線體動態平衡的重要性。粒線體動態平衡的調控機制目前仍未完全明瞭。本篇論文是以酵母菌為模式生物釐清未知的粒線體動態平衡調控機制。我們利用基因篩選，找到一個能與酵母菌中粒線體分裂蛋白Dnm1交互作用的蛋白Srv2。Srv2是一個在演化上具高度保留性的蛋白，在酵母菌中能調節肌動蛋白動態平衡及環磷酸腺苷/ 蛋白激酶A相關的訊息傳遞。實驗結果指出Srv2 能與Dnm1在粒線體上交互作用，同時也發現Srv2是透過調節肌動蛋白來維持粒線體的動態平衡。此外，剔除SRV2基因會使粒線體氧化磷酸化的功能嚴重受損。本篇論文結果指出Srv2可以藉由整合粒線體分裂蛋白及肌動蛋白動態調控來調節粒線體的動態平衡及功能。此研究提出並解釋Srv2在細胞中促進粒線體分裂的新角色，同時也是調控粒線體及細胞骨架動態平衡的蛋白。

關鍵字

酵母菌；粒線體；融合；分裂；動態平衡

並列摘要

Mitochondria are critical organelles because they produce ATP by oxidative phosphorylation and regulate survival through miscellaneous metabolisms. Mitochondria morphology changes continuously through fission, fusion and movement by various mechanisms. Disturbance of mitochondria dynamics is associated with neuronal and cardiac diseases. Mitochondria dynamics have been found and studied for decades; however, the complicated mechanisms are not fully dissolved. The goal of the study is to elucidate the underlying regulatory mechanism of mitochondria dynamics. We identified Srv2 that interacts with mitochondria fission protein Dnm1 by genetic screen. Srv2 is a highly conserved protein that regulates actin dynamics and cAMP/ PKA signaling. Our data demonstrated that Srv2 interacts with Dnm1 specifically on mitochondria. Genetic manipulation results indicated Srv2 contributes to mitochondria dynamics through its function on actin dynamics. In addition, Srv2 depletion negatively affects mitochondria respiratory activity. Our results suggest that Srv2 mediates mitochondria dynamics through its role in conjugating the fission machinery and actin assembly. This work characterized a novel pro-fission factor, and unveiled the link between mitochondria and cytoskeleton system.

並列關鍵字

Yeast ； Mitochondria ； Fission ； Fusion ； Dynamics

參考文獻

1 Vandecasteele, G., Szabadkai, G. & Rizzuto, R. Mitochondrial calcium homeostasis: mechanisms and molecules. IUBMB Life 52, 213-219, doi:10.1080/15216540152846028 (2001).

2 Ishibashi, H., Shimoda, S. & Gershwin, M. E. The immune response to mitochondrial autoantigens. Semin Liver Dis 25, 337-346, doi:10.1055/s-2005-916325 (2005).

3 Suen, D. F., Norris, K. L. & Youle, R. J. Mitochondrial dynamics and apoptosis. Genes Dev 22, 1577-1590, doi:10.1101/gad.1658508 (2008).

4 West, A. P., Shadel, G. S. & Ghosh, S. Mitochondria in innate immune responses. Nat Rev Immunol 11, 389-402, doi:10.1038/nri2975 (2011).

6 Boneh, A. Regulation of mitochondrial oxidative phosphorylation by second messenger-mediated signal transduction mechanisms. Cell Mol Life Sci 63, 1236-1248, doi:10.1007/s00018-005-5585-2 (2006).

國際替代計量

Srv2蛋白在酵母菌粒線體的動態平衡所扮演的角色

全文下載

主題瀏覽