Mitochondrial Dynamics in Type 2 Diabetes and Cancer

Williams, Michelle M.; Caino, M. Cecilia

doi:10.3389/fendo.2018.00211

Cited by 49 publications

(36 citation statements)

References 85 publications

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“…Previous studies have shown that high glucose increased the protein expression and phosphorylation of DRP1, thus further leading to the translocation from cytoplasmic to the mitochondrial and increase in mitochondrial fission [28]. Moreover, DRP1 inhibitor mdivi-1, silencing of DRP1 or mutant of phosphorylation site could inhibit mitochondrial fission and improve biochemical and histological features of diabetic complications [29,30]. In our study, we demonstrated that the diabetic condition induces mitochondrial fission and excessive ROS production in macrophages.…”

Section: Discussionsupporting

confidence: 58%

Mitochondrial ROS-induced lysosomal dysfunction impairs autophagic flux and contributes to M1 macrophage polarization in a diabetic condition

et al. 2019

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Macrophage polarization toward the M1 phenotype and its subsequent inflammatory response have been implicated in the progression of diabetic complications. Despite adverse consequences of autophagy impairment on macrophage inflammation, the regulation of macrophage autophagy under hyperglycemic conditions is incompletely understood. Here, we report that the autophagy-lysosome system and mitochondrial function are impaired in streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-stimulated RAW 264.7 cells. Mitochondrial dysfunction promotes reactive oxygen species (ROS) production and blocks autophagic flux by impairing lysosome function in macrophages under hyperglycemic conditions. Conversely, inhibition of mitochondrial ROS by Mito-TEMPO prevents HG-induced M1 macrophage polarization, and its effect is offset by blocking autophagic flux. The role of mitochondrial ROS in lysosome dysfunction and M1 macrophage polarization is also demonstrated in mitochondrial complex I defective RAW 264.7 cells induced by silencing NADH:ubiquinone oxidoreductase subunit-S4 (Ndufs4). These findings prove that mitochondrial ROS plays a key role in promoting macrophage polarization to inflammatory phenotype by impairing autophagy-lysosome system, which might provide clue to a novel treatment for diabetic complications.A mouse monocytic cell line, RAW 264.7, was obtained from ATCC and maintained in 1640 media with 10% heat-inactivated FBS, 100 U/ml penicillin and 100 mg/ml streptomycin. 1760

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Section: Discussionsupporting

confidence: 58%

Mitochondrial ROS-induced lysosomal dysfunction impairs autophagic flux and contributes to M1 macrophage polarization in a diabetic condition

et al. 2019

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“…However, the mitochondrion plays a pivotal role in many other biological processes, where it shows high variation in structure, proteomic composition and function differentiated in tissues and cell types. Hence the current great interest in mitochondria and disease, as confirmed by clinical literature 1,2,3 .…”

Section: Introductionmentioning

confidence: 91%

HmtVar: a brand-new resource for human mitochondrial variations and pathogenicity data

Preste

Vitale

Clima

et al. 2018

Preprint

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Human mitochondrial data are currently of great interest for both clinicians and researchers, due to the involvement of mitochondria in a number of physiological and pathological processes. Thanks to new sequencing technologies and modern databases, the huge amount of information about mitochondrial genome variability can be exploited to gain interesting insights into the relationship between DNA variants, phenotypes and diseases. For this reason, we have developed the new HmtVar resource, a variant-focused database which allows to explore a dataset of over 30000 human mitochondrial variants together with their pathogenicity prediction. Mitochondrial variation data, initially gathered from the HmtDB platform, are further integrated with in-house pathogenicity assessments based on wellestablished variants pathogenicity evaluation criteria, as well as with a set of additional annotations from third-party resources. This approach led to a comprehensive collection of information of crucial importance for human mitochondrial variation studies and investigation of common and rare diseases in which the mitochondrion is involved to some extent.

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“…This polyubiquitinates proteins on the outer mitochondrial membrane and degrades the damaged mitochondria, and biogenesis replenishes mitochondrial mass ( 10 ). Defective mitochondrial dynamic has been implicated in many chronic diseases, including cancer and diabetes ( 11 ).…”

Section: Mitochondrial Quality Controlmentioning

confidence: 99%

Mitochondrial Stability in Diabetic Retinopathy: Lessons Learned From Epigenetics

Kowluru

2019

Diabetes

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Diabetic retinopathy remains the leading cause of acquired blindness in working-age adults. While the cutting-edge research in the field has identified many molecular, functional, and structural abnormalities, the exact molecular mechanism of this devastating disease remains obscure. Diabetic environment drives dysfunction of the power generator of the cell and disturbs the homeostasis of mitochondrial dynamic. Mitochondrial DNA (mtDNA) is damaged, the transcription of mtDNA-encoded genes is impaired, and the electron transport chain is compromised, fueling into a vicious cycle of free radicals. The hyperglycemic milieu also alters the epigenetic machinery, and mtDNA and other genes associated with mitochondrial homeostasis are epigenetically modified, further contributing to the mitochondrial damage. Thus, mitochondria appear to have a significant role in the development of diabetic retinopathy, and unraveling the mechanism responsible for their damage as well as the role of epigenetic modifications in mitochondrial homeostasis should identify novel therapeutic targets. This will have a major impact on inhibiting/halting diabetic retinopathy and preventing the loss of vision.

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Mitochondrial Dynamics in Type 2 Diabetes and Cancer

Cited by 49 publications

References 85 publications

Mitochondrial ROS-induced lysosomal dysfunction impairs autophagic flux and contributes to M1 macrophage polarization in a diabetic condition

Mitochondrial ROS-induced lysosomal dysfunction impairs autophagic flux and contributes to M1 macrophage polarization in a diabetic condition

HmtVar: a brand-new resource for human mitochondrial variations and pathogenicity data

Mitochondrial Stability in Diabetic Retinopathy: Lessons Learned From Epigenetics

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