探究AICAR 和Metformin對粒線體動態平衡的影響

粒線體是一個高度動態平衡的胞器，經由不斷的分裂與融合可以幫助維持粒線體的型態與功能。在文獻中也可以看到參與粒線體動態平衡的蛋白會影響細胞凋亡。因此，粒線體的動態平衡與粒線體的功能和細胞的代謝反應息息相關。近期的研究發現，Metformin對許多癌症細胞皆有抑制其生長的效果，然而，AICAR也被報導過可以抑制癌細胞的生長並且影響其粒線體的功能。但是AICAR 和Metformin是否會影響粒線體的動態平衡及如何影響粒線體功能的機制尚待釐清，本篇論文將探討AICAR 和Metformin對於粒線體的動態平衡的影響。我們的實驗結果發現，AICAR會透過融合與分裂的蛋白改變粒線體的型態。此外，我們也觀察到AICAR和Metformin皆具有調控分裂與融合相關基因及蛋白的能力。最後，我們也發現AICAR會影響粒線體膜電位及粒線體氧化物質的生成。在我們的研究初步釐清AICAR 和Metformin在粒線體動態平衡的調控機制的影響，這些結果同時可以讓我們對於這兩種藥物的作用機制有更進一步的了解。

關鍵字

粒線體動態平衡

並列摘要

Mitochondria are highly dynamic organelles that play essential roles in energy supplying and cell metabolism. Dynamic fission and fusion are necessary for maintaining mitochondrial function and cell viability. Disrupted mitochondrial dynamics leads to mitochondria defect and disease. Metformin is the first-line drug for type 2 diabetes and reported to inhibit complex I in the mitochondrial respiratory chain. Previous study showed that both Metformin and 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR) promote AMPK activity and mitochondrial activity. However, the mechanisms of how AICAR and Metformin affect mitochondria remain to be examined. In this project, we aim to clarify the underlying mechanisms of whether mitochondrial dynamics is affected by AICAR and Metformin. We found AICAR caused mitochondria hyperfusion but not Metformin. Also, we monitored mitochondrial dynamics related parameters such as promotor activities of fusion and fission genes, mitochondrial dynamics related proteins and activities. Finally, we found AICAR affected mitochondrial membrane potential and superoxide production. Elucidating the effects of AICAR and Metformin not only will help us to better understand the regulation of mitochondrial dynamics, but also potential mechanisms for therapeutic drugs for related diseases.

並列關鍵字

mitochondrial dynamics ； AICAR ； Metformin

參考文獻

Alirol, E., and Martinou, J.C. (2006). Mitochondria and cancer: is there a morphological connection Oncogene 25, 4706-4716.

Andreux, P.A., Houtkooper, R.H., and Auwerx, J. (2013). Pharmacological approaches to restore mitochondrial function. Nat Rev Drug Discov 12, 465-483.

Archer, S.L. (2013). Mitochondrial dynamics--mitochondrial fission and fusion in human diseases. N Engl J Med 369, 2236-2251.

Arnold Y. Seo, A.-M.J., Debapriya Dutta, Judy C. Y. Hwang, John P. Aris and Christiaan Leeuwenburgh (2010). New insights into the role of mitochondria in aging: mitochondrial dynamics and more.

Barbour, J.A., and Turner, N. (2014). Mitochondrial stress signaling promotes cellular adaptations. Int J Cell Biol 2014, 156020.

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探究AICAR 和Metformin對粒線體動態平衡的影響

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