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Theranostics 2021Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and...
Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and invading pathogens via the lysosomal system (the vacuole in plants and yeast). Autophagy is generally induced by stress, such as oxygen-, energy- or amino acid-deprivation, irradiation, drugs, . In addition to non-selective bulk degradation, autophagy also occurs in a selective manner, recycling specific organelles, such as mitochondria, peroxisomes, ribosomes, endoplasmic reticulum (ER), lysosomes, nuclei, proteasomes and lipid droplets (LDs). This capability makes selective autophagy a major process in maintaining cellular homeostasis. The dysfunction of selective autophagy is implicated in neurodegenerative diseases (NDDs), tumorigenesis, metabolic disorders, heart failure, . Considering the importance of selective autophagy in cell biology, we systemically review the recent advances in our understanding of this process and its regulatory mechanisms. We emphasize the 'cargo-ligand-receptor' model in selective autophagy for specific organelles or cellular components in yeast and mammals, with a focus on mitophagy and ER-phagy, which are finely described as types of selective autophagy. Additionally, we highlight unanswered questions in the field, helping readers focus on the research blind spots that need to be broken.
Topics: Autophagy; Humans; Macroautophagy; Mitophagy; Organelles
PubMed: 33391472
DOI: 10.7150/thno.49860 -
Reproductive Sciences (Thousand Oaks,... Oct 2022Oocyte morphology assessment is easy to implement in any laboratory with possible quality grading prior to fertilization. At present, comprehensive oocyte morphology... (Review)
Review
Oocyte morphology assessment is easy to implement in any laboratory with possible quality grading prior to fertilization. At present, comprehensive oocyte morphology scoring is not performed as a routine procedure. However, it may augment chances for successful treatment outcomes if a correlation with certain dysmorphisms can be proven. In order to determine a correlation between oocyte morphology and treatment outcome, we performed a systematic search in PubMed and Cochrane Controlled Trials Register following PRISMA guidelines. A total of 52 articles out of 6,755 search results met the inclusion criteria. Dark colour of the cytoplasm (observed with an incidence rate of 7%), homogeneous granularity of the cytoplasm (19%) and ovoid shape of oocytes (7%) appeared to have no influence on treatment outcome. Abnormalities such as refractile bodies (10%), fragmented first polar body (37%), dark zona pellucida (9%), enlarged perivitelline space (18%) and debris in it (21%) are likely to affect the treatment outcome to some extent. Finally, cytoplasmic vacuoles (4%), centrally located cytoplasmic granularity (12%) and clusters of smooth endoplasmic reticulum (4%) negatively impact infertility treatment outcomes. Nonetheless, morphological assessment is informative rather than predictive. Adding oocyte morphology to the artificial intelligence (AI)-driven selection process may improve the precision of the algorithms. Oocyte morphology assessment can be especially useful in oocyte donation cycles, during oocyte freezing for fertility preservation and finally, objective oocyte scoring can be important in cases of very poor treatment outcome as a tool for explanation of results to the patient.
Topics: Artificial Intelligence; Humans; Infertility; Oocyte Donation; Oocytes; Zona Pellucida
PubMed: 34816375
DOI: 10.1007/s43032-021-00723-y -
Journal of Assisted Reproduction and... Jun 2023The storage and release of calcium ions (Ca2 +) in oocyte maturation and fertilization are particularly noteworthy features of the endoplasmic reticulum (ER). The ER... (Review)
Review
The storage and release of calcium ions (Ca2 +) in oocyte maturation and fertilization are particularly noteworthy features of the endoplasmic reticulum (ER). The ER is the largest organelle in the cell composed of rough ER, smooth ER, and nuclear envelope, and is the main site of protein synthesis, transport and folding, and lipid and steroid synthesis. An appropriate calcium signaling response can initiate oocyte development and embryogenesis, and the ER is the central link that initiates calcium signaling. The transition from immature oocytes to zygotes also requires many coordinated organelle reorganizations and changes. Therefore, the purpose of this review is to generalize information on the function, structure, interaction with other organelles, and spatiotemporal localization of the ER in mammalian oocytes. Mechanisms related to maintaining ER homeostasis have been extensively studied in recent years. Resolving ER stress through the unfolded protein response (UPR) is one of them. We combined the clinical problems caused by the ER in in vitro maturation (IVM), and the mechanisms of ER have been identified by single-cell RNA-seq. This article systematically reviews the functions of ER and provides a reference for assisted reproductive technology (ART) research.
Topics: Animals; Oocytes; Unfolded Protein Response; Endoplasmic Reticulum Stress; Oogenesis; Endoplasmic Reticulum; Mammals
PubMed: 37171741
DOI: 10.1007/s10815-023-02782-3 -
Signal Transduction and Targeted Therapy Mar 2023Research on obesity- and diabetes mellitus (DM)-related carcinogenesis has expanded exponentially since these two diseases were recognized as important risk factors for...
Research on obesity- and diabetes mellitus (DM)-related carcinogenesis has expanded exponentially since these two diseases were recognized as important risk factors for cancers. The growing interest in this area is prominently actuated by the increasing obesity and DM prevalence, which is partially responsible for the slight but constant increase in pancreatic cancer (PC) occurrence. PC is a highly lethal malignancy characterized by its insidious symptoms, delayed diagnosis, and devastating prognosis. The intricate process of obesity and DM promoting pancreatic carcinogenesis involves their local impact on the pancreas and concurrent whole-body systemic changes that are suitable for cancer initiation. The main mechanisms involved in this process include the excessive accumulation of various nutrients and metabolites promoting carcinogenesis directly while also aggravating mutagenic and carcinogenic metabolic disorders by affecting multiple pathways. Detrimental alterations in gastrointestinal and sex hormone levels and microbiome dysfunction further compromise immunometabolic regulation and contribute to the establishment of an immunosuppressive tumor microenvironment (TME) for carcinogenesis, which can be exacerbated by several crucial pathophysiological processes and TME components, such as autophagy, endoplasmic reticulum stress, oxidative stress, epithelial-mesenchymal transition, and exosome secretion. This review provides a comprehensive and critical analysis of the immunometabolic mechanisms of obesity- and DM-related pancreatic carcinogenesis and dissects how metabolic disorders impair anticancer immunity and influence pathophysiological processes to favor cancer initiation.
Topics: Humans; Carcinogenesis; Diabetes Mellitus; Obesity; Pancreas; Pancreatic Neoplasms; Tumor Microenvironment
PubMed: 36964133
DOI: 10.1038/s41392-023-01376-w -
The Journal of Clinical Endocrinology... Dec 2023Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women...
PURPOSE
Polycystic ovary syndrome (PCOS) is a complex genetic trait and the most common endocrine disorder of women, clinically evident in 5% to 15% of reproductive-aged women globally, with associated cardiometabolic dysfunction. Adipose tissue (AT) dysfunction appears to play an important role in the pathophysiology of PCOS even in patients who do not have excess adiposity.
METHODS
We undertook a systematic review concerning AT dysfunction in PCOS, and prioritized studies that assessed AT function directly. We also explored therapies that targeted AT dysfunction for the treatment of PCOS.
RESULTS
Various mechanisms of AT dysfunction in PCOS were identified including dysregulation in storage capacity, hypoxia, and hyperplasia; impaired adipogenesis; impaired insulin signaling and glucose transport; dysregulated lipolysis and nonesterified free fatty acids (NEFAs) kinetics; adipokine and cytokine dysregulation and subacute inflammation; epigenetic dysregulation; and mitochondrial dysfunction and endoplasmic reticulum and oxidative stress. Decreased glucose transporter-4 expression and content in adipocytes, leading to decreased insulin-mediated glucose transport in AT, was a consistent abnormality despite no alterations in insulin binding or in IRS/PI3K/Akt signaling. Adiponectin secretion in response to cytokines/chemokines is affected in PCOS compared to controls. Interestingly, epigenetic modulation via DNA methylation and microRNA regulation appears to be important mechanisms underlying AT dysfunction in PCOS.
CONCLUSION
AT dysfunction, more than AT distribution and excess adiposity, contributes to the metabolic and inflammation abnormalities of PCOS. Nonetheless, many studies provided contradictory, unclear, or limited data, highlighting the urgent need for additional research in this important field.
Topics: Humans; Female; Adult; Polycystic Ovary Syndrome; Insulin Resistance; Phosphatidylinositol 3-Kinases; Adipose Tissue; Insulin; Cytokines; Obesity; Inflammation; Glucose
PubMed: 37329216
DOI: 10.1210/clinem/dgad356 -
Gene Apr 2020Psoriasis has a complex genetic background with a strong heritable component. Herein, the present meta-analysis aims to evaluate the association of ERAP1 polymorphisms... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Psoriasis has a complex genetic background with a strong heritable component. Herein, the present meta-analysis aims to evaluate the association of ERAP1 polymorphisms with psoriasis susceptibility.
METHODS
PubMed, Web of Sciences, Scopus, and Cochrane Library databases were examined with no time limits up to March 2019, without language, age, and sex restrictions. The odds ratio (OR) and 95% confidence interval (CI) were calculated by CMA 2.0 software in a dichotomous analysis using computed effect sizes and having OR and confidence limits for each study. The subgroup analysis based on ethnicity, type of study, and genotyping method was performed.
RESULTS
Thirteen articles were involved in the meta-analysis, in details eight were cohort studies and five were case-control studies. The results showed an association between rs27524 [OR = 1.179; 95%CI: 1.081, 1.286; p < 0.001] and rs30187 [OR = 1.237; 95%CI: 1.133, 1.351; p < 0.001] polymorphisms and psoriasis susceptibility; whereas no association was detected with rs26653 [OR = 1.013; 95%CI: 0.798, 1.286; p = 0.914] and rs27044 [OR = 1.164; 95%CI: 0.982, 1.381; p = 0.080] polymorphisms. Psoriasis susceptibility in both Caucasian and Asian ethnicities was related to rs27524 polymorphism, while rs30187 and rs27044 polymorphisms were over-represented in patients belonging to Caucasian ethnicity. In addition, in cohort studies, psoriasis susceptibility was related to rs27524 polymorphism, while the associated polymorphisms were rs26653 and rs27044 in case-control studies, and rs30187 in both cohort and case-control studies.
CONCLUSIONS
These findings showed an association between rs27524 and rs30187 polymorphisms and susceptibility to psoriasis, while lack of association was obtained for rs26653 and rs27044 polymorphisms. In order to confirm our results, further studies are needed, also considering different factors, such as type of psoriasis and ethnicity.
Topics: Aminopeptidases; Animals; Endoplasmic Reticulum; Genetic Predisposition to Disease; Humans; Polymorphism, Single Nucleotide; Psoriasis
PubMed: 32006595
DOI: 10.1016/j.gene.2020.144416 -
European Journal of Investigation in... Jun 2023Endoplasmic reticulum stress (ER stress) affects many tissues and contributes to the development and severity of chronic diseases. In contrast, regular physical exercise... (Review)
Review
Endoplasmic reticulum stress (ER stress) affects many tissues and contributes to the development and severity of chronic diseases. In contrast, regular physical exercise (PE) has been considered a powerful tool to prevent and control several chronic diseases. The present systematic review aimed to evaluate the impact of different PE protocols on ER stress markers in central and peripheral tissues in rodents. The eligibility criteria were based on PICOS (population: rodents; intervention: physical exercise/physical training; control: animals that did not undergo training; outcomes: endoplasmic reticulum stress; studies: experimental). The PubMed/Medline, Science Direct, Scopus, and Scielo databases were analyzed systematically. Quality assessment was performed using SYRCLE's risk of bias tool for animal studies. The results were qualitatively synthesized. Initially, we obtained a total of 2.490 articles. After excluding duplicates, 30 studies were considered eligible. Sixteen studies were excluded for not meeting the eligibility criteria. Therefore, 14 articles were included. The PE protocol showed decreased levels/expression of markers of ER stress in the central and peripheral tissues of rodents. PE can decrease ER stress by reducing cellular stress in the cardiac, brain, and skeletal muscle tissues in rodents. However, robust PE protocols must be considered, including frequency, duration, and intensity, to optimize the PE benefits of counteracting ER stress and its associated conditions.
PubMed: 37366786
DOI: 10.3390/ejihpe13060082 -
Science China. Life Sciences Feb 2024The endoplasmic reticulum (ER), which is composed of a continuous network of tubules and sheets, forms the most widely distributed membrane system in eukaryotic cells.... (Review)
Review
The endoplasmic reticulum (ER), which is composed of a continuous network of tubules and sheets, forms the most widely distributed membrane system in eukaryotic cells. As a result, it engages a variety of organelles by establishing membrane contact sites (MCSs). These contacts regulate organelle positioning and remodeling, including fusion and fission, facilitate precise lipid exchange, and couple vital signaling events. Here, we systematically review recent advances and converging themes on ER-involved organellar contact. The molecular basis, cellular influence, and potential physiological functions for ER/nuclear envelope contacts with mitochondria, Golgi, endosomes, lysosomes, lipid droplets, autophagosomes, and plasma membrane are summarized.
Topics: Endoplasmic Reticulum; Golgi Apparatus; Cell Membrane; Mitochondria; Lysosomes; Endosomes
PubMed: 38212460
DOI: 10.1007/s11427-023-2443-9 -
Nutrients Apr 2023Tocotrienol, a type of vitamin E, is well known for its anti-cancer and other biological activities. This systematic review aims to summarize the involvement of... (Review)
Review
BACKGROUND
Tocotrienol, a type of vitamin E, is well known for its anti-cancer and other biological activities. This systematic review aims to summarize the involvement of endoplasmic reticulum stress (ERS) and subsequent unfolded protein response (UPR) as the underlying molecular mechanisms for the anticancer properties of tocotrienol.
METHOD
A comprehensive literature search was performed in March 2023 using the PubMed, Scopus, Web of Science, and EMBASE databases. In vitro, in vivo, and human studies were considered.
RESULT
A total of 840 articles were retrieved during the initial search, and 11 articles that fit the selection criteria were included for qualitative analysis. The current mechanistic findings are based solely on in vitro studies. Tocotrienol induces cancer cell growth arrest, autophagy, and cell death primarily through apoptosis but also through paraptosis-like cell death. Tocotrienol-rich fractions, including α-, γ- and δ-tocotrienols, induce ERS, as evidenced by upregulation of UPR markers and/or ERS-related apoptosis markers. Early endoplasmic reticulum calcium ion release, increased ceramide level, proteasomal inhibition, and upregulation of microRNA-190b were suggested to be essential in modulating tocotrienol-mediated ERS/UPR transduction. Nevertheless, the upstream molecular mechanism of tocotrienol-induced ERS is largely unknown.
CONCLUSION
ERS and UPR are essential in modulating tocotrienol-mediated anti-cancer effects. Further investigation is needed to elucidate the upstream molecular mechanism of tocotrienol-mediated ERS.
Topics: Humans; Tocotrienols; Endoplasmic Reticulum Stress; Unfolded Protein Response; Apoptosis; Cell Death
PubMed: 37111076
DOI: 10.3390/nu15081854 -
Frontiers in Plant Science 2022The endoplasmic reticulum (ER) stress response is triggered by any condition that disrupts protein folding and promotes the accumulation of unfolded proteins in the...
The endoplasmic reticulum (ER) stress response is triggered by any condition that disrupts protein folding and promotes the accumulation of unfolded proteins in the lumen of the organelle. In eukaryotic cells, the evolutionarily conserved unfolded protein response is activated to clear unfolded proteins and restore ER homeostasis. The recovery from ER stress is accomplished by decreasing protein translation and loading into the organelle, increasing the ER protein processing capacity and ER-associated protein degradation activity. However, if the ER stress persists and cannot be reversed, the chronically prolonged stress leads to cellular dysfunction that activates cell death signaling as an ultimate attempt to survive. Accumulating evidence implicates ER stress-induced cell death signaling pathways as significant contributors for stress adaptation in plants, making modulators of ER stress pathways potentially attractive targets for stress tolerance engineering. Here, we summarize recent advances in understanding plant-specific molecular mechanisms that elicit cell death signaling from ER stress. We also highlight the conserved features of ER stress-induced cell death signaling in plants shared by eukaryotic cells.
PubMed: 35185996
DOI: 10.3389/fpls.2022.835738