Department of Biology, Johns Hopkins University, Baltimore, MD, USA.
Semin Cell Dev Biol. 2010 Aug;21(6):582-92. doi: 10.1016/j.semcdb.2009.12.011. Epub 2010 Jan 4.
Rhomboids are an ancient and conserved family of intramembrane-cleaving proteases, a small group of proteolytic enzymes capable of hydrolyzing a peptide bond within a transmembrane helix that anchors a substrate protein to the membrane. Mitochondrial rhomboids evolved in eukaryotes to coordinate a critical aspect of cell biology, the regulation of mitochondrial membranes dynamics. This function appears to have required the emergence of a structural feature that is unique among all other rhomboids: an additional transmembrane helix (TMH) positioned at the N-terminus of six TMHs that form the core proteolytic domain of all prokaryotic and eukaryotic rhomboids. This "1+6" structure, which is shared only among mitochondrial rhomboids, defines a subfamily of rhomboids with the prototypical family member being mammalian Parl. Here, we present the findings that in 11 years have elevated mitochondrial rhomboids as the gatekeepers of mitochondrial dynamics and apoptosis; further, we discuss the aspects of their biology that are bound to introduce new paradigm shifts in our understanding of how the organelle uses this unique type of protease to govern stress, signaling to the nucleus, and other key mitochondrial activities in health and disease.
菱形蛋白酶是一个古老而保守的跨膜水解蛋白酶家族，是一小类能够水解跨膜螺旋中肽键的蛋白水解酶，该跨膜螺旋将底物蛋白锚定在膜上。线粒体菱形蛋白酶在真核生物中进化而来，以协调细胞生物学的一个关键方面，即线粒体膜动力学的调节。这一功能似乎需要出现一种独特的结构特征，这种特征在所有其他菱形蛋白酶中是独一无二的：在形成所有原核和真核菱形蛋白酶核心蛋白水解结构域的 6 个跨膜螺旋的 N 端有一个额外的跨膜螺旋（TMH）。这种“1+6”结构仅存在于线粒体菱形蛋白酶中，定义了一个菱形蛋白酶亚家族，其典型的家族成员是哺乳动物 Parl。在这里，我们介绍了 11 年来的研究结果，这些结果将线粒体菱形蛋白酶提升为线粒体动力学和细胞凋亡的守门员；此外，我们还讨论了它们的生物学特性，这些特性必将在我们理解细胞器如何利用这种独特类型的蛋白酶来控制应激、向细胞核发出信号以及在健康和疾病中进行其他关键线粒体活动方面带来新的范式转变。
