scholarly journals The Role of Posttranslational Modification and Mitochondrial Quality Control in Cardiovascular Diseases

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Jinlin Liu ◽  
Li Zhong ◽  
Rui Guo
Keyword(s):  
Quality Control ◽  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Protein Function ◽  
Therapeutic Potential ◽  
Normal Function ◽  
Future Research ◽  
Mitochondrial Quality Control ◽  
Mitochondrial Homeostasis

Cardiovascular disease (CVD) is the leading cause of death in the world. The mechanism behind CVDs has been studied for decades; however, the pathogenesis is still controversial. Mitochondrial homeostasis plays an essential role in maintaining the normal function of the cardiovascular system. The alterations of any protein function in mitochondria may induce abnormal mitochondrial quality control and unexpected mitochondrial dysfunction, leading to CVDs. Posttranslational modifications (PTMs) affect protein function by reversibly changing their conformation. This review summarizes how common and novel PTMs influence the development of CVDs by regulating mitochondrial quality control. It provides not only ideas for future research on the mechanism of some types of CVDs but also ideas for CVD treatments with therapeutic potential.

scholarly journals PINK1 deficiency impairs osteoblast differentiation through aberrant mitochondrial homeostasis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
So-Young Lee ◽  
Hyun-Ju An ◽  
Jin Man Kim ◽  
Min-Ji Sung ◽  
Do Kyung Kim ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Quality Control ◽  
Reactive Oxygen Species Production ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Mitochondrial Quality Control ◽  
Mitochondrial Homeostasis ◽  
Ovariectomized Mice ◽  
Species Production

Abstract Background PTEN-induced kinase 1 (PINK1) is a serine/threonine-protein kinase in mitochondria that is critical for mitochondrial quality control. PINK1 triggers mitophagy, a selective autophagy of mitochondria, and is involved in mitochondrial regeneration. Although increments of mitochondrial biogenesis and activity are known to be crucial during differentiation, data regarding the specific role of PINK1 in osteogenic maturation and bone remodeling are limited. Methods We adopted an ovariectomy model in female wildtype and Pink1−/− mice. Ovariectomized mice were analyzed using micro-CT, H&E staining, Masson’s trichrome staining. RT-PCR, western blot, immunofluorescence, alkaline phosphatase, and alizarin red staining were performed to assess the expression of PINK1 and osteogenic markers in silencing of PINK1 MC3T3-E1 cells. Clinical relevance of PINK1 expression levels was determined via qRT-PCR analysis in normal and osteoporosis patients. Results A significant decrease in bone mass and collagen deposition was observed in the femurs of Pink1−/− mice after ovariectomy. Ex vivo, differentiation of osteoblasts was inhibited upon Pink1 downregulation, accompanied by impaired mitochondrial homeostasis, increased mitochondrial reactive oxygen species production, and defects in mitochondrial calcium handling. Furthermore, PINK1 expression was reduced in bones from patients with osteoporosis, which supports the practical role of PINK1 in human bone disease. Conclusions In this study, we demonstrated that activation of PINK1 is a requisite in osteoblasts during differentiation, which is related to mitochondrial quality control and low reactive oxygen species production. Enhancing PINK1 activity might be a possible treatment target in bone diseases as it can promote a healthy pool of functional mitochondria in osteoblasts.

scholarly journals Efficacy of Phytocannabinoids in Epilepsy Treatment: Novel Approaches and Recent Advances

2021 ◽  
Vol 18 (8) ◽  
pp. 3993
Author(s):  
Aaron M. Farrelly ◽  
Styliani Vlachou ◽  
Konstantinos Grintzalis
Keyword(s):  
Therapeutic Potential ◽  
Significant Proportion ◽  
Future Research ◽  
Specific Reference ◽  
Undesirable Side Effect ◽  
Treatment Resistant ◽  
Current Review ◽  
Epilepsy Treatment ◽  
Clinical Environments

Epilepsy is a neurological disorder mainly characterised by recurrent seizures that affect the entire population diagnosed with the condition. Currently, there is no cure for the disease and a significant proportion of patients have been deemed to have treatment-resistant epilepsy (TRE). A patient is deemed to have TRE if two or more antiepileptic drugs (AEDs) fail to bring about seizure remission. This inefficacy of traditional AEDs, coupled with their undesirable side effect profile, has led to researchers considering alternative forms of treatment. Phytocannabinoids have long served as therapeutics with delta-9-THC (Δ9-THC) receiving extensive focus to determine its therapeutic potential. This focus on Δ9-THC has been to the detriment of analysing the plethora of other phytocannabinoids found in the cannabis plant. The overall aim of this review is to explore other novel phytocannabinoids and their place in epilepsy treatment. The current review intends to achieve this aim via an exploration of the molecular targets underlying the anticonvulsant capabilities of cannabidiol (CBD), cannabidavarin (CBDV), delta-9-tetrahydrocannabivarin (Δ9-THCV) and cannabigerol (CBG). Further, this review will provide an exploration of current pre-clinical and clinical data as it relates to the aforementioned phytocannabinoids and the treatment of epilepsy symptoms. With specific reference to epilepsy in young adult and adolescent populations, the exploration of CBD, CBDV, Δ9-THCV and CBG in both preclinical and clinical environments can guide future research and aid in the further understanding of the role of phytocannabinoids in epilepsy treatment. Currently, much more research is warranted in this area to be conclusive.

scholarly journals PINK1: A Bridge between Mitochondria and Parkinson’s Disease

Life ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 371
Author(s):  
Filipa Barroso Gonçalves ◽  
Vanessa Alexandra Morais
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Quality Control ◽  
High Energy ◽  
Common Denominator ◽  
Mitochondrial Quality Control ◽  
Mitochondrial Homeostasis ◽  
Cellular Environment ◽  
Familial Form ◽  
Mitochondrial Functions

Mitochondria are known as highly dynamic organelles essential for energy production. Intriguingly, in the recent years, mitochondria have revealed the ability to maintain cell homeostasis and ultimately regulate cell fate. This regulation is achieved by evoking mitochondrial quality control pathways that are capable of sensing the overall status of the cellular environment. In a first instance, actions to maintain a robust pool of mitochondria take place; however, if unsuccessful, measures that lead to overall cell death occur. One of the central key players of these mitochondrial quality control pathways is PINK1 (PTEN-induce putative kinase), a mitochondrial targeted kinase. PINK1 is known to interact with several substrates to regulate mitochondrial functions, and not only is responsible for triggering mitochondrial clearance via mitophagy, but also participates in maintenance of mitochondrial functions and homeostasis, under healthy conditions. Moreover, PINK1 has been associated with the familial form of Parkinson’s disease (PD). Growing evidence has strongly linked mitochondrial homeostasis to the central nervous system (CNS), a system that is replenished with high energy demanding long-lasting neuronal cells. Moreover, sporadic cases of PD have also revealed mitochondrial impairments. Thus, one could speculate that mitochondrial homeostasis is the common denominator in these two forms of the disease, and PINK1 may play a central role in maintaining mitochondrial homeostasis. In this review, we will discuss the role of PINK1 in the mitochondrial physiology and scrutinize its role in the cascade of PD pathology.

scholarly journals Editorial: Role of Mitochondrial Quality Control in Myocardial and Microvascular Physiology and Pathophysiology

2021 ◽  
Vol 12 ◽  
Author(s):  
Amanda Lochner ◽  
Hsueh-Hsiao Wang ◽  
Russel J. Reiter ◽  
Rui Guo ◽  
Hao Zhou
Keyword(s):  
Quality Control ◽  
Mitochondrial Quality Control

scholarly journals Role of the ISR-ATF4 pathway and its cross talk with Nrf2 in mitochondrial quality control

2019 ◽  
Vol 64 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Shuya Kasai ◽  
Hiromi Yamazaki ◽  
Kunikazu Tanji ◽  
Máté János Engler ◽  
Tomoh Matsumiya ◽  
...  
Keyword(s):  
Quality Control ◽  
Cross Talk ◽  
Mitochondrial Quality Control

Mitochondrial Quality Control and Restraining Innate Immunity

2020 ◽  
Vol 36 (1) ◽  
pp. 265-289
Author(s):  
Andrew T. Moehlman ◽  
Richard J. Youle
Keyword(s):  
Innate Immunity ◽  
Quality Control ◽  
Neurodegenerative Diseases ◽  
Innate Immune ◽  
Interferon Response ◽  
Mitochondrial Quality Control ◽  
Selective Autophagy ◽  
Eukaryotic Organisms ◽  
And Function

Maintaining mitochondrial health is essential for the survival and function of eukaryotic organisms. Misfunctioning mitochondria activate stress-responsive pathways to restore mitochondrial network homeostasis, remove damaged or toxic proteins, and eliminate damaged organelles via selective autophagy of mitochondria, a process termed mitophagy. Failure of these quality control pathways is implicated in the pathogenesis of Parkinson's disease and other neurodegenerative diseases. Impairment of mitochondrial quality control has been demonstrated to activate innate immune pathways, including inflammasome-mediated signaling and the antiviral cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING)–regulated interferon response. Immune system malfunction is a common hallmark in many neurodegenerative diseases; however, whether inflammation suppresses or exacerbates disease pathology is still unclear. The goal of this review is to provide a historical overview of the field, describe mechanisms of mitochondrial quality control, and highlight recent advances on the emerging role of mitochondria in innate immunity and inflammation.

Regulation of the water channel aquaporin-2 by posttranslational modification

2011 ◽  
Vol 300 (5) ◽  
pp. F1062-F1073 ◽  
Author(s):  
Hanne B. Moeller ◽  
Emma T. B. Olesen ◽  
Robert A. Fenton
Keyword(s):  
Membrane Proteins ◽  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Posttranslational Modification ◽  
Water Channel ◽  
Cellular Functions ◽  
Aquaporin 2 ◽  
Eukaryotic Membrane Proteins ◽  
Insight Into

The cellular functions of many eukaryotic membrane proteins, including the vasopressin-regulated water channel aquaporin-2 (AQP2), are regulated by posttranslational modifications. In this article, we discuss the experimental discoveries that have advanced our understanding of how posttranslational modifications affect AQP2 function, especially as they relate to the role of AQP2 in the kidney. We review the most recent data demonstrating that glycosylation and, in particular, phosphorylation and ubiquitination are mechanisms that regulate AQP2 activity, subcellular sorting and distribution, degradation, and protein interactions. From a clinical perspective, posttranslational modification resulting in protein misrouting or degradation may explain certain forms of nephrogenic diabetes insipidus. In addition to providing major insight into the function and dynamics of renal AQP2 regulation, the analysis of AQP2 posttranslational modification may provide general clues as to the role of posttranslational modification for regulation of other membrane proteins.

scholarly journals Stanniocalcin-1 Alleviates Contrast-Induced Acute Kidney Injury by Regulating Mitochondrial Quality Control via the Nrf2 Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Fei Zhao ◽  
Li-Xin Feng ◽  
Qian Liu ◽  
Hong-Shen Wang ◽  
Cheng-Yuan Tang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Quality Control ◽  
Kidney Injury ◽  
Protective Role ◽  
Mitochondrial Quality Control ◽  
Therapy Strategy ◽  
Nrf2 Signaling Pathway ◽  
Short And Long Term ◽  
Renal Tubular

Contrast-induced acute kidney injury (CI-AKI) is the third common cause of acute kidney injury (AKI), which is associated with poor short- and long-term outcomes. Currently, effective therapy strategy for CI-AKI remains lacking. Stanniocalcin-1 (STC1) is a conserved glycoprotein with antiapoptosis and anti-inflammatory functions, but the role of STC1 in controlling CI-AKI is unknown. Here, we demonstrated a protective role of STC1 in contrast-induced injury in cultured renal tubular epithelial cells and CI-AKI rat models. Recombinant human STC1 (rhSTC1) regulated mitochondrial quality control, thus suppressing contrast-induced mitochondrial damage, oxidative stress, inflammatory response, and apoptotic injury. Mechanistically, activation of the Nrf2 signaling pathway contributes critically to the renoprotective effect of STC1. Together, this study demonstrates a novel role of STC1 in preventing CI-AKI and reveals Nrf2 as a molecular target of STC1. Therefore, this study provides a promising preventive target for the treatment of CI-AKI.

scholarly journals The role of GABARAPL1/GEC1 in Autophagic Flux and Mitochondrial Quality Control in MDA-MB-436 Breast Cancer Cells

2017 ◽  
Vol 112 ◽  
pp. 107-108 ◽  
Author(s):  
Michael Boyer-Guittaut ◽  
Sooryanarayana Varambally ◽  
Victor Darley-Usmar ◽  
Jianhua Zhang
Keyword(s):  
Breast Cancer ◽  
Quality Control ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Autophagic Flux ◽  
Mitochondrial Quality Control
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