Number matters: control of mammalian mitochondrial DNA copy number

Regulation of mitochondrial biogenesis is essential for proper cellular functioning. Mitochondrial DNA （mtDNA） depletion and the resulting mitochondrial malfunction have been implicated in cancer, neurodegeneration, diabetes, aging, and many other human diseases. Although it is known that the dynamics of the mammalian mitochondrial genome are not linked with that of the nuclear genome, very little is known about the mechanism of mtDNA propagation. Nevertheless, our understanding of the mode of mtDNA replication has ad- vanced in recent years, though not without some controversies. This review summarizes our current knowledge of mtDNA copy number control in mammalian cells, while focusing on both mtDNA replication and turnover. Although mtDNA copy number is seemingly in excess, we reason that mtDNA copy number control is an important aspect of mitochondrial genetics and biogenesis and is essential for normal cellular function.     

Clinical utility of whole genome sequencing for the detection of mitochondrial genome mutations

正Genetic mitochondrial disorders are a heterogenous group of multi-system disorders caused by an imbalance in mitochondrial function (Moggio et al.,2014;Wallace,2018).In contrast to the nuclear genome,each cell contains hundreds,or even thousands,of mtDNA molecules (Veltri et al.,1990;Calvo et al., 2006).Thus,a mixture of different mtDNA sequences can co-exist within the same individual,a situation referred to as he terop las my.The level of heteroplasmy in an individual often affects the penetrance and phenotypic severity of the diseases.Consequently,detection of sequence heteroplasmy is essential for the proper clinical interpretation of mitochondrial diseases (Stewart and Chinnery,2015).     

Anterograde and Retrograde Regulation of Nuclear Genes Encoding Mitochondrial Proteins during Growth,Development, and Stress

Mitochondrial biogenesis and function in plants require the expression of over 1000 nuclear genes encoding mitochondrial proteins （NGEMPs）. The expression of these genes is regulated by tissue-specific, developmental, internal, and external stimuli that result in a dynamic organelle involved in both metabolic and a variety of signaling processes. Although the metabolic and biosynthetic machinery of mitochondria is relatively well understood, the factors that regu- late these processes and the various signaling pathways involved are only beginning to be identified at a molecular level. The molecular components of anterograde （nuclear to mitochondrial） and retrograde （mitochondrial to nuclear） signaling pathways that regulate the expression of NGEMPs interact with chloroplast-, growth-, and stress-signaling pathways in the cell at a variety of levels, with common components involved in transmission and execution of these signals. This positions mitochondria as important hubs for signaling in the cell, not only in direct signaling of mitochondrial function per se, but also in sensing and/or integrating a variety of other internal and external signals. This integrates and optimizes growth with energy metabolism and stress responses, which is required in both photosynthetic and non-photosynthetic cells.     

线粒体DNA修复系统相关酶的研究进展

线粒体DNA（mtDNA）编码线粒体电子传递系统的亚单位以及构建翻译机器所需的各种rRAN和tRNA。mtDNA编码的每一个亚单位都是线粒体完成正常的氧化磷酸化过程所必需的,因此,线粒体DNA的完整性对于生物体的生存十分重要。长期以来,人们一直认为线粒体中不存在DNA的修复。近年来在线粒体提取物中却检测到了一定数量的修复因子,提示线粒体中存在DNA的修复。主要对线粒体修复系统中相关酶的研究进展进行综述。Abstract: Mitochondrial DNA（mtDNA） encodes subunits of the mitochondrial electron transport system and the rRNAs and tRNAs required for constructing the mitochondrial tranlational machinery.Each subunit encoded by mtDNA is essential for normal oxidative phosphorylation.Thus,integrity of the mtDNA is crucial for the survival of organisms.It has long been held that there is no DNA repair in mitochondria.But in recent years,a number of repair factors have been found in mitochondrial extracts,suggesting the presence of DNA repair in mitochondria.This review summarized recent progress of enzyme in mitochondrial DNA repair processes.     

Sperm Mitochondria in Reproduction： Good or Bad and Where Do They Go？

The mitochondrion is the major energy provider to power sperm motility. In mammals, aside from the nuclear genome, mitochondrial DNA （mtDNA） also contributes to oxidative phosphorylation to impact production of ATP by coding 13 polypeptides. However, the role of sperm mitochondria in fertilization and its final fate after fertilization are still controversial. The viewpoints that sperm bearing more mtDNA will have a better fertilizing capability and that sperm mtDNA is actively eliminated during early embryogenesis are widely accepted. However, this may be not true for several mammalian species, including mice and humans. Here, we review the sperm mitochondria and their mtDNA in sperm functions, and the mechanisms of maternal mitochondrial inheritance in mammals.     

Meiosis:Recent Progress and New Opportunities

<正>Sexual reproduction in diploid organisms requires the production of haploid gametes via the process of meiosis,in which a single round of DNA replication is followed by two consecutive cell divisions(or two nuclear divisions and one cytokinesis).In the majority of known cases the proper segregation of the parental genome into gametes is accompanied and facilitated by meiotic crossover formation,which     

DNA sequencing: the key to unveiling genome

正The genome, containing total genetic material in the organism, i.e., DNA, and RNA for some viruses, encodes the information needed for all life activity. Besides the DNA in cell nucleus, mitochondrial DNA and chloroplast DNA are also important components of the genome. Using high-throughput sequencing, a tremendous amount of genomic data has been obtained. Currently, 1,704 archaeal, 26,075 bacterial,     

Chloroplast DNA Underwent Independent Selection from Nuclear Genes during Soybean Domestication and Improvement

正The chloroplast is one of the most important organs in plants because of its essential role in photosynthesis.Studies have shown that the chloroplast was once a free-living cyanobacteria and was integrated into the host species through endosymbiosis(Goksoyr.1967).after which a large number of its genes had been donated to the host nuclear genome(Heins and     

胞质异质性——人类肿瘤组织线粒体基因突变的普遍现象

为了探讨不同肿瘤组织中线粒体基因体细胞性突变的胞质异质性和同质性状态,利用32对重叠引物对149例肿瘤组织和匹配的正常组织的全线粒体基因进行PCR扩增,并同时进行时相温度梯度凝胶电泳扫描突变筛选,基因测序确定突变类型与异质状况。结果表明,不同肿瘤组织中线粒体基因体细胞性突变的异质率不同,口腔癌（65%）和食道癌（64%）具有较高的异质率,其次为乳腺癌（45.9%）。4种转换形式的发生频率Hm→Hm > Hm→Ht > Ht→Hm > Ht→Ht。碱基转换的主要转换形式为Hm→Hm,碱基颠换则以Hm→Ht。认为胞质异质性是人类肿瘤组织线粒体基因突变的普遍现象。Abstract: To explore the status of heteroplasmy and homoplasmy of Mitochondrial DNA somatic mutations in different tumors. DNA from 149 tumors and corresponding normal tissues were extracted and entire mitochondrial genome was amplified using 32 pairs of overlapping primers. The somatic mutations were screened by temporal temperature gradient gel electrophoresis and their heteroplasmic statute were identified by sequencing. The results showed that the incidence rate of heteroplasmy of mitochondrial DNA somatic mutations varies in different tumors. There is a high rate of heteroplasmic mutation in oral cancer (65%) and esophageal cancer (64%), followed by breast cancer (45%). The frequency of four transfer types is Hm (homoplasmy)→Hm (heteroplasmy) > Hm→Ht > Ht→Hm > Ht→Ht. The main transfer forms of transition and transversion mutations are Hm→Hm and Hm→Ht respectively. Heteroplasmy is a common phenomenon in mitochondrial DNA somatic mutations of human tumors.     

Gene expression of D-beta-hydroxybutyrate dehydrogenase. II. Incorporation of pre-BDH into mitochondria

beta-hydroxybutyrate dehydrogenase (BDH), a major protein located in the inner mitochondrial membrane is encoded, as most of mitochondrial proteins, in the nuclear genome. It is synthetized on the free polysomes and post-translationally imported into the mitochondria. The neosynthesized protein is a higher molecular weight precursor. The presequence is cleaved by the matrix protease to give the mature protein. The translocation across the mitochondrial membranes needs energy. The results also indicate that cytosolic factors with low molecular weight are essential in the recognition of precursor by mitochondria and to sort out newly synthetized nuclear encoded mitochondrial proteins from others nuclear encoded proteins.     

细胞核基因组和线粒体基因组的相互作用

线粒体DNA是细胞内唯一的核外遗传物质,线粒体的主要功能是合成ATP,为细胞生命活动提供直接能量。线粒体基因组与核基因组在基因、蛋白以及细胞水平上相互作用,共同保证细胞能量代谢有关的活动,维持着线粒体的正常功能和细胞的正常状态。     

The current landscape for the treatment of mitochondrial disorders

The mitochondrial organelle is crucial to the energy metabolism of the eukaryotic cell. Defects in mitochondrial function lie at the core of a wide range of disorders, including both rare primary mitochondrial disorders and more common conditions such as Parkinson's disease and diabetes. Inherited defects in mitochondrial function can be found in both the nuclear genome and the mitochondrial genome, with the latter creating unique challenges in the treatment and understanding of disease passed on through the mitochondrial genome. In this review, we will describe the limited treatment regimens currently used to alleviate primary mitochondrial disorders, as well as the potential for emerging technologies (in particular, those involving direct manipulation of the mitochondrial genome) to more decisively treat this class of disease. We will also emphasize the critical parallels between primary mitochondrial disorders and more common ailments such as cancer and diabetes.     

The role of mitochondria in the life of the nematode,Caenorhabditis elegans

Mitochondria are essential organelles involved in energy metabolism via oxidative phosphorylation. They play a vital role in diverse biological processes such as aging and apoptosis. In humans, defects in the mitochondrial respiratory chain (MRC) are responsible for or associated with a bewildering variety of diseases. The nematode Caenorhabditis elegans is a simple animal and a powerful genetic and developmental model system. In this review, we discuss how the nematode model system has contributed to our understanding of mitochondrial dynamics, of the genetics and inheritance of the mitochondrial genome, and of the consequences of nuclear and mitochondrial DNA (mtDNA) mutations. Mitochondrial respiration is vital to energy metabolism but also to other aspects of multicellular life such as aging and development. We anticipate that further significant contributions to our understanding of mitochondrial function in animal biology are forthcoming with the C. elegans model system.     

The human mitochondrial replication fork in health and disease

Mitochondria are organelles whose main function is to generate power by oxidative phosphorylation. Some of the essential genes required for this energy production are encoded by the mitochondrial genome, a small circular double stranded DNA molecule. Human mtDNA is replicated by a specialized machinery distinct from the nuclear replisome. Defects in the mitochondrial replication machinery can lead to loss of genetic information by deletion and/or depletion of the mtDNA, which subsequently may cause disturbed oxidative phosphorylation and neuromuscular symptoms in patients. We discuss here the different components of the mitochondrial replication machinery and their role in disease. We also review the mode of mammalian mtDNA replication.