McFarland R, Taylor R W, Turnbull D M
Mitochondrial Research Group, School of Neurology, Neurobiology, and Psychiatry, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom.
Curr Top Dev Biol. 2007;77:113-55. doi: 10.1016/S0070-2153(06)77005-3.
Mitochondria are ubiquitous organelles that are intimately involved in many cellular processes, but whose principal task is to provide the energy necessary for normal cell functioning and maintenance. Disruption of this energy supply can have devastating consequences for the cell, organ, and individual. Over the last two decades, mutations in both mitochondrial DNA (mtDNA) and nuclear DNA have been identified as causative in a number of well-characterized clinical syndromes, although for mtDNA mutations in particular, this relationship between genotype and phenotype is often not straightforward. Despite this, a number of epidemiological studies have been undertaken to assess the prevalence of mtDNA mutations and these have highlighted the impact that mtDNA disease has on both the community and individual families. Although there has been considerable improvement in the diagnosis of mitochondrial disorders, disappointingly this has not been matched by developments toward effective treatment. Nevertheless, our understanding of mitochondrial biology is gathering pace and progress in this area will be crucial to devising future treatment strategies. In addition to mitochondrial disease, evidence for a central role of mitochondria in other processes, such as aging and neurodegeneration, is slowly accumulating, although their role in cancer remains controversial. In this chapter, we discuss these issues and offer our own views based on our cumulative experience of investigating and managing these diseases over the last 20 years.
线粒体是普遍存在的细胞器，密切参与许多细胞过程，但其主要任务是为细胞的正常功能和维持提供所需能量。这种能量供应的中断会对细胞、器官和个体产生毁灭性后果。在过去二十年中，线粒体DNA（mtDNA）和核DNA的突变已被确定为许多特征明确的临床综合征的病因，尽管特别是对于mtDNA突变，基因型与表型之间的这种关系往往并不直接。尽管如此，已经进行了一些流行病学研究来评估mtDNA突变的患病率，这些研究突出了mtDNA疾病对社区和个体家庭的影响。尽管线粒体疾病的诊断有了相当大的改善，但令人失望的是，有效的治疗进展并未与之相匹配。然而，我们对线粒体生物学的理解正在加快步伐，这一领域的进展对于制定未来的治疗策略至关重要。除了线粒体疾病，线粒体在其他过程（如衰老和神经退行性变）中起核心作用的证据正在慢慢积累，尽管它们在癌症中的作用仍存在争议。在本章中，我们将讨论这些问题，并根据我们在过去20年中对这些疾病进行调查和管理的累积经验提出我们自己的观点。
