• BMB Reports
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• 제57권1호
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• pp.19-29
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• 2024

Mitochondrial DNA (mtDNA), a multicopy genome found in mitochondria, is crucial for oxidative phosphorylation. Mutations in mtDNA can lead to severe mitochondrial dysfunction in tissues and organs with high energy demand. MtDNA mutations are closely associated with mitochondrial and age-related disease. To better understand the functional role of mtDNA and work toward developing therapeutics, it is essential to advance technology that is capable of manipulating the mitochondrial genome. This review discusses ongoing efforts in mitochondrial genome editing with mtDNA nucleases and base editors, including the tools, delivery strategies, and applications. Future advances in mitochondrial genome editing to address challenges regarding their efficiency and specificity can achieve the promise of therapeutic genome editing.

• Interdisciplinary Bio Central
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• 제3권4호
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• pp.16.1-16.8
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• 2011

Defects in mitochondrial DNA (mtDNA) cause many human diseases and are critical factors that contribute to aging. The mechanisms of maternally-inherited mtDNA mutations are well studied. However, the role of acquired mutations during the aging process is still poorly understood. The most plausible mechanism is that increased reactive oxygen species (ROS) may affect the opening of mitochondrial voltage dependent anion channel (VDAC) and thus results in damage to mtDNA. This review focuses on recent trends in mtDNA research and the mutations that appear to be associated with increased ROS.

• Journal of Genetic Medicine
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• 제12권2호
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• pp.109-117
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• 2015

Purpose: Mitochondrial diseases are clinically and genetically heterogeneous disorders, which make their exact diagnosis and classification difficult. The purpose of this study was to identify pathogenic mitochondrial DNA (mtDNA) mutations in 2 Korean families with myoclonic epilepsy with ragged-red fibers (MERRF) and Leigh syndrome, respectively. Materials and Methods: Whole mtDNAs were sequenced by the method of mtDNA-targeted next-generation sequencing (NGS). Results: Two causative mtDNA mutations were identified from the NGS data. An m.8344A>G mutation in the tRNA-Lys gene (MT-TK) was detected in a MERRF patient (family ID: MT132), and an m.9176T>C (p.Leu217Pro) mutation in the mitochondrial ATP6 gene (MT-ATP6) was detected in a Leigh syndrome patient (family ID: MT130). Both mutations, which have been reported several times before in affected individuals, were not found in the control samples. Conclusion: This study suggests that mtDNA-targeted NGS will be helpful for the molecular diagnosis of genetically heterogeneous mitochondrial diseases with complex phenotypes.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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• pp.1737-1742
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• 2015

Background: Mitochondrial DNA (mtDNA) mutations have been shown to be associated with cancer. This study explored whether mtDNA mutations enhance cholangiocarcinoma (CCA) development in individuals. Materials and Methods: The whole mitochondrial genome sequences of 25 CCA patient tissues were determined and compared to those of white blood cells from the corresponding individuals and 12 healthy controls. The mitochondrial genome was amplified using primers from Mitoseq and compared with the Cambridge Reference Sequence. Results: A total of 161 mutations were identified in CCA tissues and the corresponding white blood cells, indicating germline origins. Sixty-five (40%) were new. Nine mutations, representing those most frequently observed in CCA were tested on the larger cohort of 60 CCA patients and 55 controls. Similar occurrence frequencies were observed in both groups. Conclusions: While the correspondence between the cancer and mitochondrial genome mutation was low, it is of interest to explore the functions of the missense mutations in a larger cohort, given the possibility of targeting mitochondria for cancer markers and therapy in the future.

• BMB Reports
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• 제52권12호
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• pp.689-694
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• 2019

Ethical and safety issues have rendered mesenchymal stem cells (MSCs) popular candidates in regenerative medicine, but their therapeutic capacity is lower than that of induced pluripotent stem cells (iPSCs). This study compared original, dental tissue-derived MSCs with re-differentiated MSCs from iPSCs (iPS-MSCs). CD marker expression in iPS-MSCs was similar to original MSCs. iPS-MSCs expressed higher in pluripotent genes, but lower levels in mesodermal genes than MSCs. In addition, iPS-MSCs did not form teratomas. All iPSCs carried mtDNA mutations; some shared with original MSCs and others not previously detected therein. Shared mutations were synonymous, while novel mutations were non-synonymous or located on RNA-encoding genes. iPS-MSCs also harbored mtDNA mutations transmitted from iPSCs. Selected iPS-MSCs displayed lower mitochondrial respiration than original MSCs. In conclusion, screening for mtDNA mutations in iPSC lines for iPS-MSCs can identify mutation-free cell lines for therapeutic applications.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9283-9289
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• 2014

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer diagnosed in children and represents approximately 25% of cancer diagnoses among those younger than 15 years of age. Materials and Methods: This study investigated alterations in the displacement loop (d-loop) region of mitochondrial DNA (mtDNA) as a risk factor and diagnostic biomarker for early detection and diagnosis of acute lymphoblastic leukemia. Using mtDNA from 23 subjects diagnosed with acute lymphoblastic leukemia, the first 450 bp of the d-loop region were amplified and successfully sequenced. Results: This revealed 132 mutations at 25 positions in this region, with a mean of 6 alterations per subject. The d-loop alterations in mtDNA in subjects were all identified as single nucleotide polymorphisms in a homoplasmic distribution pattern. Mutant alleles were observed in all subjects with individual frequency rates of up to 95%. Thirteen mutant alleles in the d-loop region of mtDNA occurred with a high frequency. Novel alleles and locations were also identified in the d-loop of mtDNA as follows: 89 G insertions (40%), 95 G insertions (13%), 182 C/T substitutions (5%), 308 C insertions (19%), and 311 C insertions (80%). The findings of this study need to be replicated to be confirmed. Conclusions: Further investigation of the relationship between mutations in mitochondrial d-loop genes and incidence of acute lymphoblastic leukemia is recommended.

• Journal of Yeungnam Medical Science
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• 제16권1호
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• pp.114-118
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• 1999

LHON은 사립체 DNA의 점돌연변이에 의해서 유발되며 11778, 3460, 14484의 세 부위가 주된 사립체 DNA 점돌연변이의 위치로 알려져 있다. 이에 저자들은 점진적인 시력 저하를 호소하면서 사립체 DNA 분석 결과 11778 점돌연변이가 확인된 LHON환자 1례를 경험하였기에 문헌고찰과 함께 보고하는 바이다.

• 생명과학회지
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• 제14권2호
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• pp.296-300
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• 2004

환자의 생조직, 얼린 조직 혹은 혈액이 없는 경우에, formalin으로 고정된 파라핀조직을 이용하여 미토콘드리아 돌연변이를 확인할 수 있는지를 조사하였다. MELAS 환자 4명의 파라핀조직을 택해 이들 조직으로부터 DNA를 추출하여 대부분의 MELAS 환자 미토콘드리아 DNA의 tRN $A^{Leu(UUR)}$ gene의 3243지역에서 발견되는 Adenine의 Cuanine으로의 염기치환을 확인하고자 하였다. 실험결과 3명의 환자에게서 이 점 돌연변이를 확인할 수 있어 이들 파라핀조직의 상태가 좋은 것으로 여겨져 미토콘드리아 DNA 돌연변이 연구에 파라핀조직을 활용할 수 있을 것으로 보인다.다.

• Animal cells and systems
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• 제8권Supplyment
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• pp.55-55
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• 2004

• BMB Reports
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• 제51권6호
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• pp.296-301
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• 2018

Mitochondrial DNA (mtDNA) mutations are often observed in various cancer types. Although the correlation between mitochondrial dysfunction and cancer malignancy has been demonstrated by several studies, further research is required to elucidate the molecular mechanisms underlying accelerated tumor development and progression due to mitochondrial mutations. We generated an mtDNA-depleted cell line, ${\rho}^0$, via long-term ethidium bromide treatment to define the molecular mechanisms of tumor malignancy induced by mitochondrial dysfunction. Mitochondrial dysfunction in ${\rho}^0$ cells reduced drug-induced cell death and decreased the expression of pro-apoptotic proteins including p53. The p53 expression was reduced by activation of nuclear $factor-{\kappa}B$ that depended on elevated levels of free calcium in $HCT116/{\rho}^0$ cells. Overall, these data provide a novel mechanism for tumor development and drug resistance due to mitochondrial dysfunction.