Koppen Mirko, Langer Thomas
Institute for Genetics and Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany.
Crit Rev Biochem Mol Biol. 2007 May-Jun;42(3):221-42. doi: 10.1080/10409230701380452.
Cell survival depends on essential processes in mitochondria. Various proteases within these organelles regulate mitochondrial biogenesis and ensure the complete degradation of excess or damaged proteins. Many of these proteases are highly conserved and ubiquitous in eukaryotic cells. They can be assigned to three functional classes: processing peptidases, which cleave off mitochondrial targeting sequences of nuclearly encoded proteins and process mitochondrial proteins with regulatory functions; ATP-dependent proteases, which either act as processing peptidases with regulatory functions or as quality-control enzymes degrading non-native polypeptides to peptides; and oligopeptidases, which degrade these peptides and mitochondrial targeting sequences to amino acids. Disturbances of protein degradation within mitochondria cause severe phenotypes in various organisms and can lead to the induction of apoptotic programmes and cell-specific neurodegeneration in mammals. After an overview of the proteolytic system of mitochondria, we will focus on versatile functions of ATP-dependent AAA proteases in the inner membrane. These conserved proteolytic machines conduct protein quality surveillance of mitochondrial inner membrane proteins, mediate vectorial protein dislocation from membranes, and, acting as processing enzymes, control ribosome assembly, mitochondrial protein synthesis, and mitochondrial fusion. Implications of these functions for cell-specific axonal degeneration in hereditary spastic paraplegia will be discussed.
细胞存活依赖于线粒体中的基本过程。这些细胞器内的各种蛋白酶调节线粒体生物合成，并确保对多余或受损蛋白质进行完全降解。其中许多蛋白酶在真核细胞中高度保守且普遍存在。它们可分为三个功能类别：加工肽酶，其切割核编码蛋白质的线粒体靶向序列并加工具有调节功能的线粒体蛋白质；ATP依赖性蛋白酶，其要么作为具有调节功能的加工肽酶，要么作为将非天然多肽降解为肽的质量控制酶；以及寡肽酶，其将这些肽和线粒体靶向序列降解为氨基酸。线粒体内蛋白质降解的紊乱在各种生物体中会导致严重的表型，并可导致哺乳动物中凋亡程序的诱导和细胞特异性神经退行性变。在概述线粒体的蛋白水解系统之后，我们将重点关注内膜中ATP依赖性AAA蛋白酶的多种功能。这些保守的蛋白水解机器对线粒体内膜蛋白进行蛋白质质量监测，介导蛋白质从膜上的矢量错位，并且作为加工酶，控制核糖体组装、线粒体蛋白质合成和线粒体融合。将讨论这些功能对遗传性痉挛性截瘫中细胞特异性轴突退变的影响。
