Mitochondrial regulation of epigenetics and its role in human diseases

Minocherhomji, Sheroy; Tollefsbol, Trygve O.; Singh, Keshav K.

doi:10.4161/epi.19547

Cited by 140 publications

(114 citation statements)

References 104 publications

(143 reference statements)

Supporting

Mentioning

102

Contrasting

Unclassified

Order By: Relevance

“…37 Furthermore, depletion of mtDNA results in significant changes in the methylation pattern of a number of nuclear genes, 38 indicating a possible effect of mitochondrial dysfunction on the epigenetic landscape of the nuclear genome. 39 We acknowledge several limitations in the present study. Although we reported effects on 2 mtDNA regions separately and performed a combined analysis of these 2 regions, we cannot extrapolate these findings to the entire mitochondrial genome.…”

Section: Discussionmentioning

confidence: 85%

Placental mitochondrial methylation and exposure to airborne particulate matter in the early life environment: An ENVIRONAGE birth cohort study

Janssen¹,

Byun²,

Gyselaers³

et al. 2015

Epigenetics

170

139

View full text Add to dashboard Cite

Abbreviations: 12S rRNA, Mitochondrial ribosomal 12S rRNA; D-loop, Displacement loop; IQR, Interquartile range; mtDNA, Mitochondrial DNA; mtDNMT1, Mitochondrial isoform of nuclear-encoded DNA methyltransferase enzyme 1;MT-RNR1, Mitochondrial region RNR1; PM, Particulate matter.Most research to date has focused on epigenetic modifications in the nuclear genome, with little attention devoted to mitochondrial DNA (mtDNA). Placental mtDNA content has been shown to respond to environmental exposures that induce oxidative stress, including airborne particulate matter (PM). Damaged or non-functioning mitochondria are specifically degraded through mitophagy, exemplified by lower mtDNA content, and could be primed by epigenetic modifications in the mtDNA. We studied placental mtDNA methylation in the context of the early life exposome. We investigated placental tissue from 381 mother-newborn pairs that were enrolled in the ENVIRONAGE birth cohort. We determined mtDNA methylation by bisulfite-pyrosequencing in 2 regions, i.e., the D-loop control region and 12S rRNA (MT-RNR1), and measured mtDNA content by qPCR. PM 2.5 exposure was calculated for each participant's home address using a dispersion model. An interquartile range (IQR) increment in PM 2.5 exposure over the entire pregnancy was positively associated with mtDNA methylation (MT-RNR1: C0.91%, P D 0.01 and D-loop: C0.21%, P D 0.05) and inversely associated with mtDNA content (relative change of ¡15.60%, P D 0.001) in placental tissue. mtDNA methylation was estimated to mediate 54% [P D 0.01 (MT-RNR1)] and 27% [P D 0.06 (D-loop)] of the inverse association between PM 2.5 exposure and mtDNA content. This study provides new insight into the mechanisms of altered mitochondrial function in the early life environment. Epigenetic modifications in the mitochondrial genome, especially in the MT-RNR1 region, substantially mediate the association between PM 2.5 exposure during gestation and placental mtDNA content, which could reflect signs of mitophagy and mitochondrial death.

show abstract

Section: Discussionmentioning

confidence: 85%

Placental mitochondrial methylation and exposure to airborne particulate matter in the early life environment: An ENVIRONAGE birth cohort study

Janssen¹,

Byun²,

Gyselaers³

et al. 2015

Epigenetics

170

139

View full text Add to dashboard Cite

show abstract

“…Mitochondrial DNA encodes 13 genes, but their gene expression exhibited no obvious changes after LPS challenge. The proteins encoded by the 13 mitochondrial genes are incorporated into respiratory complexes I, IV and V (Minocherhomji et al, 2012). We further investigated the activities of these complexes.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide markedly changes glucose metabolism and mitochondrial function in the longissimus muscle of pigs

Sun

Huang

Yin

et al. 2016

Animal

View full text Add to dashboard Cite

Most previous studies on the effects of lipopolysaccharide (LPS) in pigs focused on the body's immune response, and few reports paid attention to body metabolism changes. To better understand the glucose metabolism changes in skeletal muscle following LPS challenge and to clarify the possible mechanism, 12 growing pigs were employed. Animals were treated with either 2 ml of saline or 15 µg/kg BW LPS, and samples were collected 6 h later. The glycolysis status and mitochondrial function in the longissimus dorsi (LD) muscle of pigs were analyzed. The results showed that serum lactate content and NADH content in LD muscle significantly increased compared with the control group. Most glycolysis-related genes expression, as well as hexokinase, pyruvate kinase and lactic dehydrogenase activity, in LD muscle was significantly higher compared with the control group. Mitochondrial complexes I and IV significantly increased, while mitochondrial ATP concentration markedly decreased. Significantly increased calcium content in the mitochondria was observed, and endoplasm reticulum (ER) stress has been demonstrated in the present study. The results showed that LPS treatment markedly changes glucose metabolism and mitochondrial function in the LD muscle of pigs, and increased calcium content induced by ER stress was possibly involved. The results provide new clues for clarifying metabolic diseases in muscle induced by LPS.Keywords: lipopolysaccharide, mitochondria, glycolysis, pig, inflammation ImplicationsSkeletal muscle is the primary tissue responsible for wholebody energy metabolism. In the current study, we designed the experiment to investigate the effect of lipopolysaccharide (LPS) treatment on muscle energy metabolism in pigs. The results indicated that LPS treatment significantly changed glycolysis level and mitochondrial function in the longissimus dorsi (LD) muscle of pigs, and increased calcium content induced by endoplasm reticulum stress was possibly involved. Understanding these underlying mechanisms may provide new therapeutic strategies for treating metabolic diseases induced by LPS in muscle.

show abstract

“…Lamarck's ideas could also accommodate a dominant role for epigenetics and horizontal gene transfer as factors that could facilitate tumor progression (176,177). In addition to nuclear epigenetic events involving acetylation and phosphorylations, mitochondria are also recognized as a powerful extra nuclear epigenetic system (159,(178)(179)(180). Other epigenetic phenomena such as cytomegalovirus infection, cell fusion and horizontal gene transfer can also contribute to cancer progression and metastasis (147,159,(181)(182)(183)(184).…”

Section: Cancer Progression Is More Consistent With Lamarckian Than Dmentioning

confidence: 99%

Cancer as a Metabolic Disease: Implications for Novel Therapeutics

Seyfried¹

2013

AACR Education book

View full text Add to dashboard Cite

Mitochondrial regulation of epigenetics and its role in human diseases

Cited by 140 publications

References 104 publications

Placental mitochondrial methylation and exposure to airborne particulate matter in the early life environment: An ENVIRONAGE birth cohort study

Placental mitochondrial methylation and exposure to airborne particulate matter in the early life environment: An ENVIRONAGE birth cohort study

Lipopolysaccharide markedly changes glucose metabolism and mitochondrial function in the longissimus muscle of pigs

Cancer as a Metabolic Disease: Implications for Novel Therapeutics

Contact Info

Product

Resources

About