Fu G K, Markovitz D M
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0640, USA.
Biochemistry. 1998 Feb 17;37(7):1905-9. doi: 10.1021/bi970928c.
LON proteases, which are ATP-dependent and exhibit ATPase activity, are found in bacteria, yeast, and humans. In Escherichia coli, LON is known to regulate gene expression by targeting specific regulatory proteins for degradation. The yeast and human LON proteins are encoded in the nucleus but localize to the mitochondrial matrix. In yeast, LON has been shown to be essential for the maintenance of the integrity of the mitochondrial genome. E. coli Lon has long been known to bind DNA, but we have only recently demonstrated that it binds preferentially to a specific TG-rich double-stranded sequence. We now show that human LON recognizes a very similar site in both the light and heavy chain promoters of the mitochondrial genome, in a region which is involved in regulating both DNA replication and transcription. Unlike E. coli Lon, however, human LON specifically binds to the TG-rich element only when it is presented in the context of a single DNA strand. These findings suggest that the human LON protease might regulate mitochondrial DNA replication and/or gene expression using site-specific, single-stranded DNA binding to target the degradation of regulatory proteins binding to adjacent sites in mitochondrial promoters.
LON蛋白酶是ATP依赖性的，并具有ATP酶活性，存在于细菌、酵母和人类中。在大肠杆菌中，LON已知通过靶向特定的调节蛋白进行降解来调控基因表达。酵母和人类的LON蛋白在细胞核中编码，但定位于线粒体基质。在酵母中，LON已被证明对于维持线粒体基因组的完整性至关重要。长期以来已知大肠杆菌Lon能结合DNA，但我们直到最近才证明它优先结合特定的富含TG的双链序列。我们现在表明，人类LON在线粒体基因组的轻链和重链启动子中识别一个非常相似的位点，该区域参与调控DNA复制和转录。然而，与大肠杆菌Lon不同的是，人类LON仅在其呈现于单链DNA的情况下才特异性结合富含TG的元件。这些发现表明，人类LON蛋白酶可能通过位点特异性的单链DNA结合来靶向降解结合在线粒体启动子相邻位点的调节蛋白，从而调控线粒体DNA复制和/或基因表达。
