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.

中文翻译：

---

线粒体内的蛋白质降解：AAA蛋白酶和其他肽酶的多功能活性。

细胞存活取决于线粒体的基本过程。这些细胞器中的各种蛋白酶调节线粒体的生物发生，并确保过量或受损蛋白质的完全降解。这些蛋白酶中的许多在真核细胞中是高度保守的并且普遍存在。它们可分为三类功能：加工肽酶，可切割核编码蛋白的线粒体靶向序列；加工具有调节功能的线粒体蛋白；ATP依赖性蛋白酶，可作为具有调节功能的加工肽酶，也可作为将非天然多肽降解为肽的质量控制酶；寡肽酶，它们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会导致各种生物体出现严重的表型，并可能导致哺乳动物凋亡程序的诱导和细胞特异性神经变性。概述了线粒体的蛋白水解系统后，我们将重点研究内膜中ATP依赖的AAA蛋白酶的多功能功能。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，介导载体蛋白从膜上脱位，并作为加工酶，控制核糖体装配，线粒体蛋白合成和线粒体融合。将讨论这些功能对遗传性痉挛性截瘫的细胞特异性轴突变性的影响。