Human COQ8A (ADCK3) andSaccharomyces cerevisiaeCoq8p (collectively COQ8) are UbiB family proteins essential for mitochondrial coenzyme Q (CoQ) biosynthesis. However, the biochemical activity of COQ8 and its direct role in CoQ production remain unclear, in part due to lack of known endogenous regulators of COQ8 function and of effective small molecules for probing its activityin vivo.Here, we demonstrate that COQ8 possesses evolutionarily conserved ATPase activity that is activated by binding to membranes containing cardiolipin and by phenolic compounds that resemble CoQ pathway intermediates. We further create an analog-sensitive version of Coq8p and reveal that acute chemical inhibition of its endogenous activity in yeast is sufficient to cause respiratory deficiency concomitant with CoQ depletion. Collectively, this work defines lipid and small-molecule modulators of an ancient family of atypical kinase-like proteins and establishes a chemical genetic system for further exploring the mechanistic role of COQ8 in CoQ biosynthesis.

中文翻译：

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保守的脂质和小分子调制的COQ8揭示了古代激酶样UbiB家族的监管。

人COQ8A（ADCK3）和啤酒酵母Coq8p（统称为COQ8）是线粒体辅酶Q（CoQ）生物合成必不可少的UbiB家族蛋白。然而，COQ8的生化活性及其在CoQ产生中的直接作用仍不清楚，部分原因是缺乏已知的内源性COQ8调节剂和有效的小分子在体内探测其活性。在这里，我们证明了COQ8具有进化上保守的ATPase。通过与含有心磷脂的膜结合以及类似于CoQ途径中间体的酚类化合物激活的活性。我们进一步创建了Coq8p的类似物敏感版本，并揭示了其在酵母中的内源性活性的急性化学抑制作用足以引起伴随CoQ耗竭的呼吸不足。总的来说，