Fernández-Moreno M A, Bornstein B, Petit N, Garesse R
Departamento de Bioquímica, Facultad de Medicina, Instituto de Investigaciones Biomédicas "Alberto Sols" CSIC-UAM, Universidad Autónoma de Madrid, c/ Arzobispo Morcillo 4, Madrid, 28029, Spain.
Mol Genet Metab. 2000 Nov;71(3):481-95. doi: 10.1006/mgme.2000.3083.
Mitochondria are with very few exceptions ubiquitous organelles in eukaryotic cells where they are essential for cell life and death. Mitochondria play a central role not only in a variety of metabolic pathways including the supply of the bulk of cellular ATP through oxidative phosphorylation (OXPHOS), but also in complex processes such as development, apoptosis, and aging. Mitochondria contain their own genome that is replicated and expressed within the organelle. It encodes 13 polypeptides all of them components of the OXPHOS system, and thus, the integrity of the mitochondrial DNA (mtDNA) is critical for cellular energy supply. In the past 12 years more than 50 point mutations and around 100 rearrangements in the mtDNA have been associated with human diseases. Also in recent years, several mutations in nuclear genes that encode structural or regulatory factors of the OXPHOS system or the mtDNA metabolism have been described. The development of increasingly powerful techniques and the use of cellular and animal models are opening new avenues in the study of mitochondrial medicine. The detailed molecular characterization of the effects produced by different mutations that cause mitochondrial cytopathies will be critical for designing rational therapeutic strategies for this group of devastating diseases.
线粒体是真核细胞中普遍存在的细胞器，极少数情况除外，它们对细胞的生死存亡至关重要。线粒体不仅在多种代谢途径中发挥核心作用，包括通过氧化磷酸化（OXPHOS）提供大部分细胞ATP，还在诸如发育、凋亡和衰老等复杂过程中发挥作用。线粒体含有自己的基因组，该基因组在细胞器内进行复制和表达。它编码13种多肽，这些多肽都是OXPHOS系统的组成部分，因此，线粒体DNA（mtDNA）的完整性对于细胞能量供应至关重要。在过去12年中，mtDNA中的50多种点突变和约100种重排与人类疾病相关。近年来，也描述了一些编码OXPHOS系统或mtDNA代谢的结构或调节因子的核基因中的突变。越来越强大的技术的发展以及细胞和动物模型的使用为线粒体医学研究开辟了新途径。对导致线粒体细胞病变的不同突变所产生影响的详细分子特征描述，对于设计针对这组毁灭性疾病的合理治疗策略至关重要。
