Phylogenetic tree analysis for Bali Cattle based on partial sequence 16S rRNA Mitochondrial DNA

Mitochondria DNA (mtDNA) as a source of genetic information based on the maternal genome, can provide important information for phylogenetic analysis and evolutionary biology. The objective of this study was to analyze the phylogenetic tree of Bali cattle with seven gene bank references (Bos indicus, Bos taurus, Bos frontalis, and Bos grunniens) based on partial sequence 16S rRNA mitochondria DNA. The Bayesian phylogenetic tree was constructed using BEAST 2.4. and visualization in Figtree 1.4.4 (tree.bio.ed.ac.uk/software/figtree/). The best model of evolution was carried out using jModelTest 2.1.7. The most optimal was the evolutionary models GTR + I + G with p-inv (I) 0,1990 and gamma shape 0.1960. The main result indicated that the Bali cattle were grouped into Bos javanicus. Phylogenetic analysis also successfully classifying Bos javanicus, Bos indicus, Bos taurus, Bos frontalis and Bos grunniens. These results will complete information about Bali cattle and useful for the preservation and conservation strategies of Indonesian animal genetic resources.

Loss of mpv17 affected early embryonic development via mitochondria dysfunction in zebrafish

MVP17 encodes a mitochondrial inner-membrane protein, and mutation of human MVP17 can cause mitochondria DNA depletion syndrome (MDDS). However, the underlying function of mpv17 is still elusive. Here, we developed a new mutant with mpv17 knockout by using the CRISPR/Cas9 system. The mpv17−/− zebrafish showed developmental defects in muscles, liver, and energy supply. The mpv17−/− larvae hardly survived beyond a month, and they showed abnormal growth during the development stage. Abnormal swimming ability was also found in the mpv17−/− zebrafish. The transmission electron microscope (TEM) observation indicated that the mpv17−/− zebrafish underwent severe mitochondria dysfunction and the disorder of mitochondrial cristae. As an energy producer, the defects of mitochondria significantly reduced ATP content in mpv17−/− zebrafish, compared to wild-type zebrafish. We hypothesized that the disorder of mitochondria cristae was contributed to the dysfunction of muscle and liver in the mpv17−/− zebrafish. Moreover, the content of major energy depot triglycerides (TAG) was decreased dramatically. Interestingly, after rescued with normal exogenous mitochondria by microinjection, the genes involved in the TAG metabolism pathway were recovered to a normal level. Taken together, this is the first report of developmental defects in muscles, liver, and energy supply via mitochondria dysfunction, and reveals the functional mechanism of mpv17 in zebrafish.

Role of Mitochondria in Neurodegenerative Diseases: From an Epigenetic Perspective

Mitochondria, the centers of energy metabolism, have been shown to participate in epigenetic regulation of neurodegenerative diseases. Epigenetic modification of nuclear genes encoding mitochondrial proteins has an impact on mitochondria homeostasis, including mitochondrial biogenesis, and quality, which plays role in the pathogenesis of neurodegenerative diseases like Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. On the other hand, intermediate metabolites regulated by mitochondria such as acetyl-CoA and NAD+, in turn, may regulate nuclear epigenome as the substrate for acetylation and a cofactor of deacetylation, respectively. Thus, mitochondria are involved in epigenetic regulation through bidirectional communication between mitochondria and nuclear, which may provide a new strategy for neurodegenerative diseases treatment. In addition, emerging evidence has suggested that the abnormal modification of mitochondria DNA contributes to disease development through mitochondria dysfunction. In this review, we provide an overview of how mitochondria are involved in epigenetic regulation and discuss the mechanisms of mitochondria in regulation of neurodegenerative diseases from epigenetic perspective.

Mitochondria-Targeted Nanomedicine for Enhanced Efficacy of Cancer Therapy

Nanomedicines have been designed and developed to deliver anticancer drugs or exert anticancer therapy more selectively to tumor sites. Recent investigations have gone beyond delivering drugs to tumor tissues or cells, but to intracellular compartments for amplifying therapy efficacy. Mitochondria are attractive targets for cancer treatment due to their important functions for cells and close relationships to tumor occurrence and metastasis. Accordingly, multifunctional nanoplatforms have been constructed for cancer therapy with the modification of a variety of mitochondriotropic ligands, to trigger the mitochondria-mediated apoptosis of tumor cells. On this basis, various cancer therapeutic modalities based on mitochondria-targeted nanomedicines are developed by strategies of damaging mitochondria DNA (mtDNA), increasing reactive oxygen species (ROS), disturbing respiratory chain and redox balance. Herein, in this review, we highlight mitochondria-targeted cancer therapies enabled by nanoplatforms including chemotherapy, photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), sonodynamic therapy (SDT), radiodynamic therapy (RDT) and combined immunotherapy, and discussed the ongoing challenges.

Mitochondrial Mutations and Genetic Factors Determining NAFLD Risk

NAFLD (non-alcoholic fatty liver disease) is a widespread liver disease that is often linked with other life-threatening ailments (metabolic syndrome, insulin resistance, diabetes, cardiovascular disease, atherosclerosis, obesity, and others) and canprogress to more severe forms, such as NASH (non-alcoholic steatohepatitis), cirrhosis, and HCC (hepatocellular carcinoma). In this review, we summarized and analyzed data about single nucleotide polymorphism sites, identified in genes related to NAFLD development and progression. Additionally, the causative role of mitochondrial mutations and mitophagy malfunctions in NAFLD is discussed. The role of mitochondria-related metabolites of the urea cycle as a new non-invasive NAFLD biomarker is discussed. While mitochondria DNA mutations and SNPs (single nucleotide polymorphisms) canbe used as effective diagnostic markers and target for treatments, age and ethnic specificity should be taken into account.

Mitochondria-DNA copy-number and incident venous thromboembolism among middle-aged women: a population-based cohort study

Venous thromboembolism (VTE) is the third most common cardiovascular disease. Low amount of mitochondrial DNA copy number (mtDNA-CN) has been associated with arterial cardiovascular disease (CVD) and reflects mitochondrial dysfunctions. However, whether mtDNA-CN is associated with VTE has not been determined. To examine the association between mtDNA-CN and incident VTE among middle-aged women. 6917 women aged 50–64 years, followed for 20 years in the Women’s Health In the Lund Area (WHILA) study. DNA samples for mtDNA quantification were available from 2521 women. Quantification of mtDNA-CN was performed using a well-optimized droplet digital PCR method. After exclusions of women with anticoagulant treatment, women living in nursing homes, and women who were diagnosed with cancer, stroke, VTE, or coronary heart disease at baseline, a cohort of 2117 women remained for analysis. Cox regression was used to analyze the relationship between mtDNA-CN and time to VTE (hazard ratio = HR). In total, 87 women were diagnosed with VTE during follow-up, corresponding to an incidence rate of 2.8 per 1000 person-years. Neither crude nor adjusted HR for mtDNA-CN were significantly associated with incident VTE. A sensitivity analysis with inclusion of excluded women did not change the results. MtDNA-CN was not significantly associated with VTE. The present study suggests that mtDNA-CN, reflecting mitochondrial dysfunction, should not be considered a biomarker that plays a major role for developing VTE. However, due to limited study size we may not exclude minor associations.

DNA Repair Pathways in Cancer Therapy and Resistance

DNA repair pathways are triggered to maintain genetic stability and integrity when mammalian cells are exposed to endogenous or exogenous DNA-damaging agents. The deregulation of DNA repair pathways is associated with the initiation and progression of cancer. As the primary anti-cancer therapies, ionizing radiation and chemotherapeutic agents induce cell death by directly or indirectly causing DNA damage, dysregulation of the DNA damage response may contribute to hypersensitivity or resistance of cancer cells to genotoxic agents and targeting DNA repair pathway can increase the tumor sensitivity to cancer therapies. Therefore, targeting DNA repair pathways may be a potential therapeutic approach for cancer treatment. A better understanding of the biology and the regulatory mechanisms of DNA repair pathways has the potential to facilitate the development of inhibitors of nuclear and mitochondria DNA repair pathways for enhancing anticancer effect of DNA damage-based therapy.

Variations in Hybrid Combinations Lead to Differences in Mitochondrial Inheritance

BackgroundWhile tilapia are the second most farmed group of fish in the world, the Oreochromis niloticus (♀) × Oreochromis aureus (♂) hybrid is one of the most frequently observed tilapia crosses in China. Based on its conservative nature and maternal inheritance pattern, mitochondrial DNA is often used in kinship analysis. Evidence of paternal inheritance has been noted in some animal species. ResultsThe mitochondrial CoI and Cytb genes, and D-loop gene regions of Oreochromis niloticus and Oreochromis aureus fish were sequenced and aligned to their orthogonal and backcrossed offspring. As evidence of paternal mitochondria DNA inheritance was found, the whole mitochondrial genome was then sequenced. Results showed that in the Oreochromis niloticus (♀) × Oreochromis aureus (♂) hybrids, certain fish shared 92.88% of the maternal mitochondria genome, and 99.86% with the paternal mitochondria genome. This implied that there was paternal mtDNA inheritance. However, all Oreochromis niloticus (♂) × Oreochromis aureus (♀) hybrids had 100% identical mitochondria genome with their female parent. ConclusionsThe study showed that while paternal mtDNA inheritance occurred in the Oreochromis niloticus (♀) × Oreochromis aureus (♂) hybrid, this did not happen in Oreochromis niloticus (♂) × Oreochromis aureus (♀) offspring. This implies that in hybrid species, different hybridization combinations might provide an explanation for paternal mtDNA inheritance pattern.

Electronic Cigarettes Induce Mitochondrial DNA Damage and Trigger TLR 9 (Toll-Like Receptor 9)-Mediated Atherosclerosis

Objective: Electronic cigarette (e-cig) use has recently been implicated in promoting atherosclerosis. In this study, we aimed to investigate the mechanism of e-cig exposure accelerated atherosclerotic lesion development. Approach and Results: Eight-week-old ApoE − /− mice fed normal laboratory diet were exposed to e-cig vapor (ECV) for 2 hours/day, 5 days/week for 16 weeks. We found that ECV exposure significantly induced atherosclerotic lesions as examined by Oil Red O staining and greatly upregulated TLR9 (toll-like receptor 9) expression in classical monocytes and in the atherosclerotic plaques, which the latter was corroborated by enhanced TLR9 expression in human femoral artery atherosclerotic plaques from e-cig smokers. Intriguingly, we found a significant increase of oxidative mitochondria DNA lesion in the plasma of ECV-exposed mice. Administration of TLR9 antagonist before ECV exposure not only alleviated atherosclerosis and the upregulation of TLR9 in plaques but also attenuated the increase of plasma levels of inflammatory cytokines, reduced the plaque accumulation of lipid and macrophages, and decreased the frequency of blood CCR2 + classical monocytes. Surprisingly, we found that cytoplasmic mitochondrial DNA isolated from ECV extract-treated macrophages can enhance TLR9 activation in reporter cells and the induction of inflammatory cytokine could be suppressed by TLR9 inhibitor in macrophages. Conclusions: E-cig increases level of damaged mitochondrial DNA in circulating blood and induces the expression of TLR9, which elevate the expression of proinflammatory cytokines in monocyte/macrophage and consequently lead to atherosclerosis. Our results raise the possibility that intervention of TLR9 activation is a potential pharmacological target of ECV-related inflammation and cardiovascular diseases.