Mitoepigenetics: The different shades of grey

Ghosh, Sourav; Singh, Keshav K.; Sengupta, Shantanu; Scaria, Vinod

doi:10.1016/j.mito.2015.09.003

Cited by 33 publications

(24 citation statements)

References 60 publications

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“…It is not known whether these small changes in DNA methylation reflect changes in gene expression. Regardless, they may serve as a biomarker of a cascade of other biological reactions [43][44][45], such as MDP regulation [38].…”

Section: Discussionmentioning

confidence: 99%

Platelet mitochondrial DNA methylation predicts future cardiovascular outcome in adults with overweight and obesity

et al. 2020

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Background: The association between obesity and cardiovascular disease (CVD) is proven, but why some adults with obesity develop CVD while others remain disease-free is poorly understood. Here, we investigated whether mitochondrial DNA (mtDNA) methylation in platelets is altered prior to CVD development in a population of adults with overweight and obesity. Methods: We devised a nested case-control study of 200 adults with overweight or obesity who were CVD-free at baseline, of whom 84 developed CVD within 5 years, while 116 remained CVD-free. Platelet mtDNA was isolated from plasma samples at baseline, and mtDNA methylation was quantified in mitochondrially encoded cytochrome-C-oxidase I (MT-CO1; nt6797 and nt6807), II (MT-CO2; nt8113 and nt8117), and III (MT-CO3; nt9444 and nt9449); tRNA leucine 1 (MT-TL1; nt3247 and nt3254); D-loop (nt16383); tRNA phenylalanine (MT-TF; nt624); and light-strand-originof-replication (MT-OLR; nt5737, nt5740, and nt5743) by bisulfite-pyrosequencing. Logistic regression was used to estimate the contribution of mtDNA methylation to future CVD risk. ROC curve analysis was used to identify the optimal mtDNA methylation threshold for future CVD risk prediction. A model was generated incorporating methylation at three loci (score 0, 1, or 2 according to 0, 1, or 2-3 hypermethylated loci, respectively), adjusted for potential confounders, such as diastolic and systolic blood pressure, fasting blood glucose, and cholesterol ratio. mtDNA methylation at MT-CO1 nt6807 (OR = 1.08, 95% CI 1.02-1.16; P = 0.014), MT-CO3 nt9444 (OR = 1.22, 95% CI 1.02-1.46, P = 0.042), and MT-TL1 nt3254 (OR = 1.30, 95% CI 1.05-1.61, P = 0.008) was higher at baseline in those who developed CVD by follow-up, compared with those who remained CVD-free. Combined use of the three loci significantly enhanced risk prediction, with hazard ratios of 1.38 (95% CI 0.68-2.78) and 2.68 (95% CI 1.41-5.08) for individuals with score 1 or 2, respectively (P = 0.003). Methylation at these sites was independent of conventional CVD risk factors, including inflammation markers, fasting blood glucose concentration, and blood pressure. Conclusions: Methylations of MT-CO1, MT-CO3, and MT-TL1 are, together, strong predictors of future CVD incidence. Since methylation of these mtDNA domains was independent of conventional CVD risk factors, these markers may represent a novel intrinsic predictor of CVD risk in adults with overweight and obesity.

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Section: Discussionmentioning

confidence: 99%

Platelet mitochondrial DNA methylation predicts future cardiovascular outcome in adults with overweight and obesity

et al. 2020

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“…Methylation is a known feature of mitochondrial DNA (see 41), and methylation patterns can be observed as changes in the nanopore electrical signal 42 . Due to the lack of information about epigenetic patterns from de novo nanopore sequencing, this dataset is provided without additional epigenetic analysis as a source of discovery for other researchers.…”

Section: Discussionmentioning

confidence: 99%

Annotated mitochondrial genome with Nanopore R9 signal for Nippostrongylus brasiliensis

et al. 2017

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Nippostrongylus brasiliensis, a nematode parasite of rodents, has a parasitic life cycle that is an extremely useful model for the study of human hookworm infection, particularly in regards to the induced immune response. The current reference genome for this parasite is highly fragmented with minimal annotation, but new advances in long-read sequencing suggest that a more complete and annotated assembly should be an achievable goal. We de-novo assembled a single contig mitochondrial genome from N. brasiliensis using MinION R9 nanopore data. The assembly was error-corrected using existing Illumina HiSeq reads, and annotated in full (i.e. gene boundary definitions without substantial gaps) by comparing with annotated genomes from similar parasite relatives. The mitochondrial genome has also been annotated with a preliminary electrical consensus sequence, using raw signal data generated from a Nanopore R9 flow cell.

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“…Vital cellular functions such as regulation of energy production, maintenance of redox status and cell growth are controlled by mitochondria 1–3 . Shifts in mitochondrial function may lead to impaired biosynthetic pathways, dysregulated cellular signal transduction pathways, and modulation of gene transcription as well as chromatin structure 4, 5 . Alterations in mitochondrial mass or functions influence cellular functions, proliferation, and survival, and have been shown to affect metastasis as well as the clinical outcome of patients with cancer 2, 6 .…”

Section: Introductionmentioning

confidence: 99%

Cryptolepine inhibits melanoma cell growth through coordinated changes in mitochondrial biogenesis, dynamics and metabolic tumor suppressor AMPKα1/2-LKB1

Pal

Prasad

Katiyar

2017

Sci Rep

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Mitoepigenetics: The different shades of grey

Cited by 33 publications

References 60 publications

Platelet mitochondrial DNA methylation predicts future cardiovascular outcome in adults with overweight and obesity

Platelet mitochondrial DNA methylation predicts future cardiovascular outcome in adults with overweight and obesity

Annotated mitochondrial genome with Nanopore R9 signal for Nippostrongylus brasiliensis

Cryptolepine inhibits melanoma cell growth through coordinated changes in mitochondrial biogenesis, dynamics and metabolic tumor suppressor AMPKα1/2-LKB1

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