COMP-prohibitin 2 interaction maintains mitochondrial homeostasis and controls smooth muscle cell identity

Jia, Yiting; Wang, Meili; Mao, Chenfeng; Yu, Fang; Wang, Yingbao; Xiao, Rui; Jiang, Changtao; Zheng, Lemin; Xu, Qingbo; Zheng, Ming; Fu, Yi; Hu, Qinghua; Kong, Wei

doi:10.1038/s41419-018-0703-x

Cited by 24 publications

(21 citation statements)

References 66 publications

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“…Maintaining mitochondrial homeostasis may be a potential protective factor for VSMCs to resist osteoblast-like phenotypic transitions (Jia et al, 2018;Zhu et al, 2019). In VSMCs, supplementation with metformin restores b-GP-mediated mitochondrial biogenesis in VSMCs, such as increased mitochondrial DNA copy number, up-regulated mitochondrial membrane potential (MMP), and mitochondrial biosynthesis gene expression (Ma et al, 2019).…”

Section: Vascular Calcificationmentioning

confidence: 99%

Metformin and Vascular Diseases: A Focused Review on Smooth Muscle Cell Function

Mingying

et al. 2020

Front. Pharmacol.

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Metformin has been used in diabetes for more than 60 years and has excellent safety in the therapy of human type 2 diabetes (T2D). There is growing evidence that the beneficial health effects of metformin are beyond its ability to improve glucose metabolism. Metformin not only reduces the incidence of cardiovascular diseases (CVD) in T2D patients, but also reduces the burden of atherosclerosis (AS) in pre-diabetes patients. Vascular smooth muscle cells (VSMCs) function is an important factor in determining the characteristics of the entire arterial vessel. Its excessive proliferation contributes to the etiology of several types of CVD, including AS, restenosis, and pulmonary hypertension. Current studies show that metformin has a beneficial effect on VSMCs function. Therefore, this review provides a timely overview of the role and molecular mechanisms by which metformin acts through VSMCs to protect CVD.

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Section: Vascular Calcificationmentioning

confidence: 99%

Metformin and Vascular Diseases: A Focused Review on Smooth Muscle Cell Function

Mingying

et al. 2020

Front. Pharmacol.

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“…To further investigate whether the reduction in SMC contraction is attributable to mitochondrial dysfunction, we performed mitochondrial transplantation experiments as described previously 20,25 . Mitochondria isolated from donor cells were transplanted into the mitochondriadeleted recipient cells (Fig.…”

Section: Mitochondrial Transplantation With Healthy Mitochondria Restmentioning

confidence: 99%

Hypermethylation of mitochondrial DNA in vascular smooth muscle cells impairs cell contractility

et al. 2020

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Vascular smooth muscle cell (SMC) from arterial stenotic-occlusive diseases is featured with deficiency in mitochondrial respiration and loss of cell contractility. However, the regulatory mechanism of mitochondrial genes and mitochondrial energy metabolism in SMC remains elusive. Here, we described that DNA methyltransferase 1 (DNMT1) translocated to the mitochondria and catalyzed D-loop methylation of mitochondrial DNA in vascular SMCs in response to platelet-derived growth factor-BB (PDGF-BB). Mitochondrial-specific expression of DNMT1 repressed mitochondrial gene expression, caused functional damage, and reduced SMC contractility. Hypermethylation of mitochondrial D-loop regions were detected in the intima-media layer of mouse carotid arteries subjected to either cessation of blood flow or mechanical endothelial injury, and also in vessel specimens from patients with carotid occlusive diseases. Likewise, the ligated mouse arteries exhibited an enhanced mitochondrial binding of DNMT1, repressed mitochondrial gene expression, defects in mitochondrial respiration, and impaired contractility. The impaired contractility of a ligated vessel could be restored by ex vivo transplantation of DNMT1-deleted mitochondria. In summary, we discovered the function of DNMT1-mediated mitochondrial D-loop methylation in the regulation of mitochondrial gene transcription. Methylation of mitochondrial D-loop in vascular SMCs contributes to impaired mitochondrial function and loss of contractile phenotype in vascular occlusive disease.

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“…PHBs are ubiquitously expressed in various cells and mainly localized in mitochondria, but also expressed in nuclei and cell membranes [ 79 ]. PHBs contribute to mitochondrial biology [ 79 ] and homeostasis [ 80 , 81 ] by regulating ROS formation, protein degradation, mitochondrial morphology, and the oxidative phosphorylation (OXPHOS) complex [ 82 ]. The expression of PHB1 was decreased by Cholix in hepatocytes.…”

Section: Prohibitin Binding and Mitochondrial Dysfunctionmentioning

confidence: 99%

Cell Death Signaling Pathway Induced by Cholix Toxin, a Cytotoxin and eEF2 ADP-Ribosyltransferase Produced by Vibrio cholerae

Ogura

Yahiro

Moss

2020

Toxins

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Pathogenic microorganisms produce various virulence factors, e.g., enzymes, cytotoxins, effectors, which trigger development of pathologies in infectious diseases. Cholera toxin (CT) produced by O1 and O139 serotypes of Vibrio cholerae (V. cholerae) is a major cytotoxin causing severe diarrhea. Cholix cytotoxin (Cholix) was identified as a novel eukaryotic elongation factor 2 (eEF2) adenosine-diphosphate (ADP)-ribosyltransferase produced mainly in non-O1/non-O139 V. cholerae. The function and role of Cholix in infectious disease caused by V. cholerae remain unknown. The crystal structure of Cholix is similar to Pseudomonas exotoxin A (PEA) which is composed of an N-terminal receptor-recognition domain and a C-terminal ADP-ribosyltransferase domain. The endocytosed Cholix catalyzes ADP-ribosylation of eEF2 in host cells and inhibits protein synthesis, resulting in cell death. In a mouse model, Cholix caused lethality with severe liver damage. In this review, we describe the mechanism underlying Cholix-induced cytotoxicity. Cholix-induced apoptosis was regulated by mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) signaling pathways, which dramatically enhanced tumor necrosis factor-α (TNF-α) production in human liver, as well as the amount of epithelial-like HepG2 cancer cells. In contrast, Cholix induced apoptosis in hepatocytes through a mitochondrial-dependent pathway, which was not stimulated by TNF-α. These findings suggest that sensitivity to Cholix depends on the target cell. A substantial amount of information on PEA is provided in order to compare/contrast this well-characterized mono-ADP-ribosyltransferase (mART) with Cholix.

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COMP-prohibitin 2 interaction maintains mitochondrial homeostasis and controls smooth muscle cell identity

Cited by 24 publications

References 66 publications

Metformin and Vascular Diseases: A Focused Review on Smooth Muscle Cell Function

Metformin and Vascular Diseases: A Focused Review on Smooth Muscle Cell Function

Hypermethylation of mitochondrial DNA in vascular smooth muscle cells impairs cell contractility

Cell Death Signaling Pathway Induced by Cholix Toxin, a Cytotoxin and eEF2 ADP-Ribosyltransferase Produced by Vibrio cholerae

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