Tissue-specific differences in mitochondrial DNA content in type 2 diabetes

Hsieh, Ching‐Chuan; Weng, Shao‐Wen; Liou, Chia‐Wei; Lin, Tsu-Kung; Chen, Jin‐Bor; Tiao, Mao‐Meng; Hung, Yun-Ting; Chen, I.-Ya; Huang, Wen-Te; Wang, Pei‐Wen

doi:10.1016/j.diabres.2011.01.010

Cited by 29 publications

(21 citation statements)

References 16 publications

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“…24 Although mtDNA copy number can vary among organs, changes in mtDNA levels in muscle have been reported to reflect comparable processes in other tissues, such as blood leukocytes and hepatocytes. 25 Another noteworthy finding of the present study is that the levels of intracellular inflammatory markers were significantly decreased. A mounting body of evidence suggests that mitochondrial dysfunction induced by oxidative stress and chronic low-grade inflammation plays a key role in the development of insulin resistance and the pathogenesis of type 2 DM.…”

supporting

confidence: 54%

Korean Red Ginseng Protects Against Mitochondrial Damage and Intracellular Inflammation in an Animal Model of Type 2 Diabetes Mellitus

Park

Shim

Cho

et al. 2018

Journal of Medicinal Food

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Korean red ginseng (KRG), a heat-processed Korean ginseng (Panax ginseng C.A. Meyer), has been used as a traditional medicine for its beneficial effects on hyperglycemia. This study aimed to investigate whether the antidiabetic action of KRG in an animal model of type 2 diabetes mellitus (DM) is partly mediated by prevention of mitochondrial dysfunction and intracellular inflammation. Four-week-old C57BL/KsJ db/db mice (a genetic animal model of obese type 2 DM) and C57BL/KsJ db/+ mice were divided into three groups: db/+ mice (normoglycemic control group, n = 8), db/db mice (untreated DM group, n = 8), and db/db mice with KRG administration (KRG-treated DM group, n = 8). After 12 weeks, metabolic parameters of fasting blood glucose concentrations, hemoglobin A1c (HbA1c) level, insulin level, lipid profile, and leukocyte count were determined using high-performance liquid chromatography. Mitochondrial DNA (mtDNA) copy number and inflammatory marker (interleukin-6, cyclooxygenase-2, and C-reactive protein) expression levels were measured in skeletal muscle tissue using quantitative real-time PCR analysis. After 12 weeks of KRG treatment at 100 mg/kg, the fasting glucose, HbA1c, insulin, and low-density lipoprotein cholesterol concentrations were lower, whereas mtDNA copy numbers were higher in the KRG-treated DM group than in the untreated DM group. Compared with the untreated DM group, the messenger RNA expression levels of mitochondrial biogenesis-related transcription factors and inflammatory markers were lower in the KRG-treated DM group. In conclusion, KRG had a beneficial effect on the metabolic profile by preserving mitochondrial function and protecting against intracellular inflammation.

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supporting

confidence: 54%

Korean Red Ginseng Protects Against Mitochondrial Damage and Intracellular Inflammation in an Animal Model of Type 2 Diabetes Mellitus

Park

Shim

Cho

et al. 2018

Journal of Medicinal Food

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“…These shifts in the levels of glucose have been associated with high levels of IL-6, TNF-α, and molecule ICAM-1, which have been related to coronary heart disease, atherosclerosis, and vascular inflammation . Here, it is convenient to mention that mtDNA content varies in the different tissues of the body, which can help explain the different levels of damage observed in the diabetic or prediabetic patient (Hsieh et al, 2011). In a recent and interesting publication Pinti et al (2014) reported an increase in the levels of plasma mtDNA associated with the age of the studied people.…”

Section: Perspectivementioning

confidence: 96%

Circulating cell-free mitochondrial DNA as the probable inducer of early endothelial dysfunction in the prediabetic patient

Alvarado-Vásquez¹

2015

Experimental Gerontology

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“…Earlier studies have reported reduced SIRT3 levels and reduced mtDNA content in diabetic patients (7,48,49). Similarly, OPA1 mutations are linked to instability of mtDNA (50,51).…”

Section: Opa1 Is Acetylated At Lysmentioning

confidence: 99%

SIRT3 Deacetylates and Activates OPA1 To Regulate Mitochondrial Dynamics during Stress

Samant

Zhang

Hong

et al. 2014

Molecular and Cellular Biology

357

267

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f Mitochondrial morphology is regulated by the balance between two counteracting mitochondrial processes of fusion and fission. There is significant evidence suggesting a stringent association between morphology and bioenergetics of mitochondria. Morphological alterations in mitochondria are linked to several pathological disorders, including cardiovascular diseases. The consequences of stress-induced acetylation of mitochondrial proteins on the organelle morphology remain largely unexplored. Here we report that OPA1, a mitochondrial fusion protein, was hyperacetylated in hearts under pathological stress and this posttranslational modification reduced the GTPase activity of the protein. The mitochondrial deacetylase SIRT3 was capable of deacetylating OPA1 and elevating its GTPase activity. Mass spectrometry and mutagenesis analyses indicated that in SIRT3-deficient cells OPA1 was acetylated at lysine 926 and 931 residues. Overexpression of a deacetylation-mimetic version of OPA1 recovered the mitochondrial functions of OPA1-null cells, thus demonstrating the functional significance of K926/931 acetylation in regulating OPA1 activity. Moreover, SIRT3-dependent activation of OPA1 contributed to the preservation of mitochondrial networking and protection of cardiomyocytes from doxorubicin-mediated cell death. In summary, these data indicated that SIRT3 promotes mitochondrial function not only by regulating activity of metabolic enzymes, as previously reported, but also by regulating mitochondrial dynamics by targeting OPA1.

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Tissue-specific differences in mitochondrial DNA content in type 2 diabetes

Cited by 29 publications

References 16 publications

Korean Red Ginseng Protects Against Mitochondrial Damage and Intracellular Inflammation in an Animal Model of Type 2 Diabetes Mellitus

Korean Red Ginseng Protects Against Mitochondrial Damage and Intracellular Inflammation in an Animal Model of Type 2 Diabetes Mellitus

Circulating cell-free mitochondrial DNA as the probable inducer of early endothelial dysfunction in the prediabetic patient

SIRT3 Deacetylates and Activates OPA1 To Regulate Mitochondrial Dynamics during Stress

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