Lestienne P, Bataillé N
U 298 INSERM, CHRU Angers, France.
Biomed Pharmacother. 1994;48(5-6):199-214. doi: 10.1016/0753-3322(94)90134-1.
We review the main features of human mitochondrial function and structure, and in particular mitochondrial transcription, translation, and replication cycles. Furthermore, some pecularities such as mitochondria's high polymorphism, the existence of mitochondrial pseudogenes, and the various considerations to take into account when studying mitochondrial diseases will also be mentioned. Mitochondrial syndromes mostly affecting the nervous system have, during the past few years, been associated with mitochondrial DNA (mt DNA) alterations such as deletions, duplications, mutations and depletions. We suggest a possible classification of mitochondrial diseases according to the kind of mt DNA mutations: structural mitochondrial gene mutation as in LHON (Leber's Hereditary Optic Neuropathy) and NARP (Neurogenic muscle weakness, Ataxia and Retinitis Pigmentosa) as well as some cases of Leigh's syndrome; transfer RNA and ribosomal RNA mitochondrial gene mutation as in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Strokelike Episodes) or MERRF (Myoclonic Epilepsy with Ragged Red Fibers) or deafness with aminoglycoside; structural with transfer RNA mitochondrial gene mutations as observed in large-scale deletions or duplications in Kearns-Sayre syndrome, Pearson's syndrome, diabetes mellitus with deafness, and CPEO (Chronic Progressive External Ophtalmoplegia). Depletions of the mt DNA may also be classified in this category. Even though mutations are generally maternally inherited, most of the deletions are sporadic. However, multiple deletions or depletions may be transmitted in a mendelan trait which suggests that nuclear gene products play a primary role in these processes. The relationship between a mutation and a particular phenotype is far from being fully understood. Gene dosage and energic threshold, which are tissue-specific, appear to be the best indicators. However, the recessive or dominant behavior of both the wild type or the mutated genome appears to play a significant role, which can be verified with in vitro studies.
我们回顾了人类线粒体功能和结构的主要特征，特别是线粒体转录、翻译和复制周期。此外，还将提及一些特殊之处，如线粒体的高度多态性、线粒体假基因的存在，以及研究线粒体疾病时需要考虑的各种因素。在过去几年中，主要影响神经系统的线粒体综合征已与线粒体DNA（mtDNA）改变相关，如缺失、重复、突变和耗竭。我们根据mtDNA突变的类型提出了一种可能的线粒体疾病分类：结构线粒体基因突变，如在Leber遗传性视神经病变（LHON）和神经源性肌无力、共济失调和色素性视网膜炎（NARP）以及一些 Leigh 综合征病例中；线粒体转运RNA和核糖体RNA基因突变，如在线粒体脑肌病伴乳酸酸中毒和卒中样发作（MELAS）、肌阵挛性癫痫伴破碎红纤维（MERRF）或氨基糖苷类致聋中；结构与线粒体转运RNA基因突变，如在Kearns-Sayre综合征、Pearson综合征、糖尿病伴耳聋和慢性进行性眼外肌麻痹（CPEO）中的大规模缺失或重复中观察到的。mtDNA的耗竭也可归为此类。尽管突变通常是母系遗传的，但大多数缺失是散发性的。然而，多个缺失或耗竭可能以孟德尔性状传递，这表明核基因产物在这些过程中起主要作用。突变与特定表型之间的关系远未完全理解。组织特异性的基因剂量和能量阈值似乎是最好的指标。然而，野生型或突变基因组的隐性或显性行为似乎也起重要作用，这可以通过体外研究得到证实。
