NADH dehydrogenase (ubiquinone) Fe-S protein 8，簡稱NDUFS8，為粒線體酵素複合體I中由細胞核基因體組表現的核心蛋白。此蛋白具有兩個含高度保留半胱胺酸的模組，可幫助形成兩組[4Fe-4S]的鐵硫中心，而且這些鐵硫中心在酵素複合體I電子傳遞中扮演重要的角色。NDUFS8的缺失是第一個被證實與Leigh症候群有關聯性的酵素複合體I之成分蛋白，其也陸續被證實與躁鬱症以及粒線體腦肌病等神經疾病相關。在本研究中，我們是利用核酸干擾 (RNAi) 技術抑制T-REx293細胞中NDUFS8的表現，藉此來探討NDUFS8產生缺失後在人類粒線體酵素複合體I所造成的影響。實驗結果顯示，在只含有半乳糖的培養條件下，NDUFS8受到抑制的細胞生長速度會比在只含有葡萄糖的培養條件下之細胞還慢，甚至導致細胞死亡。在酵素複合體I的功能分析中也顯示，減少NDUFS8的表現會使酵素複合體I的結構完整性以及穩定性受到影響，而其氧化NADH的能力也因此下降。此外，它也使得粒線體膜電位下降，進而影響細胞內ATP的生成量減少。同時NDUFS8的表現量受到抑制也使得酵素複合體III和IV之次單元的蛋白表現量和其結構之穩定受到影響。由以上實驗結果推論，NDUFS8在維持酵素複合體I的功能和結構中扮演了關鍵的角色，甚至也參與了穩定呼吸體的結構。此外為了研究NDUFS8鐵硫簇的模組中具有的高度保留之8個半胱胺酸，我們利用定點突變的方式，探討這些半胱胺酸產生變異是否對於粒線體酵素複合體I執行功能或是結構穩定產生影響。實驗結果與在Rhodobacter capsulatus、Neurospora crassa和Escherichia coli等物種發現的結果不一樣。將人類的NDUFS8鐵硫中心模組中的單一個半胱胺酸突變成為絲胺酸，是不會影響NDUFS8被運輸至粒線體，也不會影響酵素複合體I的結構穩定性以及其活性功能。

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