Low expression of Mfn2 is associated with mitochondrial damage and apoptosis in the placental villi of early unexplained miscarriage

Pang, Wenjuan; Zhang, Y.; Zhao, Na; Darwiche, Sophie S.; Fu, Xiangning; Xiang, Wenpei

doi:10.1016/j.placenta.2013.03.013

Cited by 34 publications

(28 citation statements)

References 32 publications

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“…Low expression of Mfn2 mRNA and protein in early SCNT placentae, found here, caused aberrant mitochondrial morphology (Figs 2 and 3), as well as low expression of BNIP3L protein, which is responsible for selective elimination of damaged mitochondria (Fig 3B). These results overlap with those previously observed in human placentae collected from “unexplained” early miscarriages [21], as well as mouse dendritic cells mutant for Mfn2 [25], and mouse embryonic fibroblast-Mfn2 knockout cells [26]. …”

Section: Discussionsupporting

confidence: 88%

“…In fact, Chan and colleagues have shown that mice deficient in Mfn2 die in mid-gestation, mostly as a result of specific and severe disruptions in the placental trophoblast binuclear cell layer [20]. Moreover, human extravillous trophoblastic cells from early miscarriages exhibit very low expression of mitochondrial fusion protein (Mfn2) and damaged mitochondria [21]. …”

Section: Discussionmentioning

confidence: 99%

“…Chan et al found that mice deficient in Mfn2 died in mid-gestation mainly due to placental abnormalities, particularly a severe disruption of the trophoblast binuclear cell layer [20]. Besides that, it has been shown that deficient expression of Mfn2 in human trophoblastic cells might be responsible for “unexplained” early miscarriage [21]. Loss-of-function models of Mfn2 in embryonic mouse fibroblasts display distinct types of fragmented, damaged, and immature mitochondria, attributable to a marked reduction in mitochondrial function [22].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Deregulated Expression of Mitochondrial Proteins Mfn2 and Bcnl3L in Placentae from Sheep Somatic Cell Nuclear Transfer (SCNT) Conceptuses

et al. 2017

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In various animal species, the main cause of pregnancy loss in conceptuses obtained by somatic cell nuclear transfer (SCNT) are placental abnormalities. Most abnormalities described in SCNT pregnancies (such as placentomegaly, reduced vascularisation, hypoplasia of trophoblastic epithelium) suggest that placental cell degeneration may be triggered by mitochondrial failure. We hypothesized that placental abnormalities of clones obtained by SCNT are related to mitochondrial dysfunction. To test this, early SCNT and control (CTR, from pregnancies obtained by in vitro fertilization) placentae were collected from pregnant ewes (at day 20 and 22 of gestation) and subjected to morphological, mRNA and protein analysis. Here, we demonstrated swollen and fragmented mitochondria and low expression of mitofusin 2 (Mfn2), the protein which plays a crucial role in mitochondrial functionality, in SCNT early placentae. Furthermore, reduced expression of the Bcnl3L/Nix protein, which plays a crucial role in selective elimination of damaged mitochondria, was observed and reflected by the accumulation of numerous damaged mitochondria in SCNT placental cells. Likely, this accumulation of damaged organelles led to uncontrolled apoptosis in SCNT placentae, as demonstrated by the high number of apoptotic bodies, fragmented cytoplasm, condensed chromatin, lack of integrity of the nuclear membrane and the perturbed mRNA expression of apoptotic genes (BCL2 and BAX). In conclusion, our data indicate that deregulated expression of Mfn2 and Bcnl3L is responsible for placental abnormalities in SCNT conceptuses. Our results suggest that some nuclear genes, that are involved in the regulation of mitochondrial function, do not work well and consequently this influence the function of mitochondria.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Deregulated Expression of Mitochondrial Proteins Mfn2 and Bcnl3L in Placentae from Sheep Somatic Cell Nuclear Transfer (SCNT) Conceptuses

et al. 2017

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“…4). MFN-2 helps to regulate the morphology of mitochondria by controlling the fusion process and also participates in the regulation of MPP, cellular metabolism and apoptosis [43], [44]. It is noteworthy that the overexpression of MLN64 was maintained only 48 h. The observation that the expression of the MFN-2 protein was decreased under these conditions suggests that MLN64 overexpression had a profound impact on mitochondrial dynamics.…”

Section: Discussionmentioning

confidence: 99%

MLN64 induces mitochondrial dysfunction associated with increased mitochondrial cholesterol content

et al. 2017

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MLN64 is a late endosomal cholesterol-binding membrane protein that has been implicated in cholesterol transport from endosomal membranes to the plasma membrane and/or mitochondria, in toxin-induced resistance, and in mitochondrial dysfunction. Down-regulation of MLN64 in Niemann-Pick C1 deficient cells decreased mitochondrial cholesterol content, suggesting that MLN64 functions independently of NPC1. However, the role of MLN64 in the maintenance of endosomal cholesterol flow and intracellular cholesterol homeostasis remains unclear. We have previously described that hepatic MLN64 overexpression increases liver cholesterol content and induces liver damage. Here, we studied the function of MLN64 in normal and NPC1-deficient cells and we evaluated whether MLN64 overexpressing cells exhibit alterations in mitochondrial function. We used recombinant-adenovirus-mediated MLN64 gene transfer to overexpress MLN64 in mouse liver and hepatic cells; and RNA interference to down-regulate MLN64 in NPC1-deficient cells. In MLN64-overexpressing cells, we found increased mitochondrial cholesterol content and decreased glutathione (GSH) levels and ATPase activity. Furthermore, we found decreased mitochondrial membrane potential and mitochondrial fragmentation and increased mitochondrial superoxide levels in MLN64-overexpressing cells and in NPC1-deficient cells. Consequently, MLN64 expression was increased in NPC1-deficient cells and reduction of its expression restore mitochondrial membrane potential and mitochondrial superoxide levels. Our findings suggest that MLN64 overexpression induces an increase in mitochondrial cholesterol content and consequently a decrease in mitochondrial GSH content leading to mitochondrial dysfunction. In addition, we demonstrate that MLN64 expression is increased in NPC cells and plays a key role in cholesterol transport into the mitochondria.

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“…The supernatants were collected and stored at a low temperature. The ATP levels were assayed through ATP assay kit (Pang et al 2013) (Nanjing JianCheng Bioengineering Institute, China). The results were analyzed by UV/Visible Spectrophotometer (UV-VIS, Thermo Fisher Scientific, USA).…”

Section: Atp Levelsmentioning

confidence: 99%

Antibacterial mechanism and activities of black pepper chloroform extract

Zou

Chen

2015

J Food Sci Technol

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Black pepper extracts reportedly inhibit food spoilage and food pathogenic bacteria. This study explored the antimicrobial activity of black pepper chloroform extract (BPCE) against Escherichia coli and Staphylococcus aureus. The antibacterial mechanism of BPCE was elucidated by analyzing the cell morphology, respiratory metabolism, pyruvic acid content, and ATP levels of the target bacteria. Scanning electron micrographs showed that the bacterial cells were destroyed and that plasmolysis was induced. BPCE inhibited the tricarboxylic acid pathway of the bacteria. The extract significantly increased pyruvic acid concentration in bacterial solutions and reduced ATP level in bacterial cells. BPCE destroyed the permeability of the cell membrane, which consequently caused metabolic dysfunction, inhibited energy synthesis, and triggered cell death.

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Low expression of Mfn2 is associated with mitochondrial damage and apoptosis in the placental villi of early unexplained miscarriage

Cited by 34 publications

References 32 publications

Deregulated Expression of Mitochondrial Proteins Mfn2 and Bcnl3L in Placentae from Sheep Somatic Cell Nuclear Transfer (SCNT) Conceptuses

Deregulated Expression of Mitochondrial Proteins Mfn2 and Bcnl3L in Placentae from Sheep Somatic Cell Nuclear Transfer (SCNT) Conceptuses

MLN64 induces mitochondrial dysfunction associated with increased mitochondrial cholesterol content

Antibacterial mechanism and activities of black pepper chloroform extract

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