Initially discovered as a protease responsible for degradation of misfolded or damaged proteins, the mitochondrial Lon protease (Lonp1) turned out to be a multifaceted enzyme, that displays at least three different functions (proteolysis, chaperone activity, binding of mtDNA) and that finely regulates several cellular processes, within and without mitochondria. Indeed, LONP1 in humans is ubiquitously expressed, and is involved in regulation of response to oxidative stress and, heat shock, in the maintenance of mtDNA, in the regulation of mitophagy. Furthermore, its proteolytic activity can regulate several biochemical pathways occurring totally or partially within mitochondria, such as TCA cycle, oxidative phosphorylation, steroid and heme biosynthesis and glutamine production. Because of these multiple activities, Lon protease is highly conserved throughout evolution, and mutations occurring in its gene determines severe diseases in humans, including a rare syndrome characterized by Cerebral, Ocular, Dental, Auricular and Skeletal anomalies (CODAS). Finally, alterations of LONP1 regulation in humans can favor tumor progression and aggressiveness, further highlighting the crucial role of this enzyme in mitochondrial and cellular homeostasis.

线粒体Lon蛋白酶（Lonp1）最初被发现是负责降解错误折叠或损坏的蛋白质的蛋白酶，后来发现它是一种多方面的酶，具有至少三种不同的功能（蛋白水解，分子伴侣活性，mtDNA结合），并能精细调节线粒体内外的几个细胞过程。实际上，人类中的LONP1被广泛表达，并参与对氧化应激和热休克的调节，以及mtDNA的维持和线粒体的调节。此外，其蛋白水解活性可以调节线粒体内全部或部分发生的几种生化途径，例如TCA循环，氧化磷酸化，类固醇和血红素的生物合成以及谷氨酰胺产生。由于有这些多种活动，Lon蛋白酶在整个进化过程中都是高度保守的，其基因中发生的突变决定了人类的严重疾病，包括一种罕见的以脑，眼，牙齿，耳廓和骨骼异常（CODAS）为特征的综合征。最后，人类中LONP1调控的改变可以促进肿瘤的进展和侵袭性，进一步突显了该酶在线粒体和细胞稳态中的关键作用。