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Autophagy Oct 2021Polycystic ovary syndrome (PCOS) is a unification of endocrine and metabolic disorders and has become immensely prevalent among women of fertile age. The prime organ... (Review)
Review
Polycystic ovary syndrome (PCOS) is a unification of endocrine and metabolic disorders and has become immensely prevalent among women of fertile age. The prime organ affected in PCOS is the ovary and its distressed functioning elicits disturbed reproductive outcomes. In the ovary, macroautophagy/autophagy performs a pivotal role in directing the chain of events starting from oocytes origin until its fertilization. Recent discoveries demonstrate a significant role of autophagy in the pathogenesis of PCOS. Defective autophagy in the follicular cells during different stages of follicles is observed in the PCOS ovary. Exploring different autophagy pathways provides a platform for predicting the possible cause of altered ovarian physiology in PCOS. In this review, we have emphasized autophagy's role in governing follicular development under normal circumstances and in PCOS, including significant abnormalities associated with PCOS such as anovulation, hyperandrogenemia, metabolic disturbances, and related abnormality. So far, few studies have linked autophagy and PCOS and propose its essential role in PCOS progression. However, detailed knowledge in this area is lacking. Here we have summarized the latest knowledge related to autophagy associated with PCOS. This review's main objective is to provide a background of autophagy in the ovary, its possible connection with PCOS and suggested a novel proposal for future studies to aid a better understanding of PCOS pathogenesis.: AE: androgen excess; AF: antral follicle; AKT/PKB: AKT serine/threonine kinase; AMH: anti-Mullerian hormone; AMPK: AMP-activated protein kinase; ATG: autophagy-related; BCL2: BCL2 apoptosis regulator; BECN1: beclin 1; BMP: bone morphogenetic protein; CASP3: caspase 3; CL: corpus luteum; CYP17A1/P450C17: cytochrome P450 family 17 subfamily A member 1; CYP19A1: cytochrome P450 family 19 subfamily A member 1; DHEA: dehydroepiandrosterone; EH: endometrial hyperplasia; FF: follicular fluid; FOXO: forkhead box O; FSH: follicle stimulating hormone; GC: granulosa cell; GDF: growth differentiation factor; HA: hyperandrogenemia; HMGB1: high mobility group box 1; IGF1: insulin like growth factor 1; INS: insulin; IR: insulin resistance; LHCGR/LHR: luteinizing hormone/choriogonadotropin receptor; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAPK/ERK: mitogen-activated protein kinase; MAPK8/JNK: mitogen-activated protein kinase 8; MTOR: mechanistic target of rapamycin kinase; MTORC: mechanistic target of rapamycin complex; NAFLD: nonalcoholic fatty liver disease; NFKB: nuclear factor kappa B; OLR1/LOX-1: oxidized low density lipoprotein receptor 1; oxLDL: oxidized low-density lipoproteins; PA: palmitic acid; PCOS: polycystic ovary syndrome; PF: primary follicle; PGC: primordial germ cell; PI3K: phosphoinositide 3-kinase; PMF: primordial follicle; ROS: reactive oxygen species; RP: resting pool; SIRT1: sirtuin 1; SQSTM1/p62: sequestosome 1; T2DM: type 2 diabetes mellitus; TC: theca cell; TUG1: taurine up-regulated 1.
Topics: Autophagy; Diabetes Mellitus, Type 2; Dissent and Disputes; Female; Humans; Phosphatidylinositol 3-Kinases; Polycystic Ovary Syndrome
PubMed: 34161185
DOI: 10.1080/15548627.2021.1938914 -
Autophagy Oct 2017Discovery of yeast autophagy-related (ATG) genes and subsequent identification of their homologs in other organisms have enabled researchers to investigate physiological... (Review)
Review
Discovery of yeast autophagy-related (ATG) genes and subsequent identification of their homologs in other organisms have enabled researchers to investigate physiological functions of macroautophagy/autophagy using genetic techniques. Specific identification of autophagy-related structures is important to evaluate autophagic activity, and specific ablation of autophagy-related genes is a critical means to determine the requirements of autophagy. Here, we review currently available mouse models, particularly focusing on autophagy (and mitophagy) indicator models and systemic autophagy-related gene-knockout mouse models.
Topics: Animals; Autophagy; Autophagy-Related Proteins; Humans; Mice; Mice, Knockout; Mitochondria; Mitophagy; Saccharomyces cerevisiae; Signal Transduction
PubMed: 28820286
DOI: 10.1080/15548627.2017.1343770 -
Seminars in Cell & Developmental Biology Feb 2020Metabolic reprogramming in tumours is now recognized as a hallmark of cancer, participating both in tumour growth and cancer progression. Cancer cells develop global... (Review)
Review
Metabolic reprogramming in tumours is now recognized as a hallmark of cancer, participating both in tumour growth and cancer progression. Cancer cells develop global metabolic adaptations allowing them to survive in the low oxygen and nutrient tumour microenvironment. Among these metabolic adaptations, cancer cells use glycolysis but also mitochondrial oxidations to produce ATP and building blocks needed for their high proliferation rate. Another particular adaptation of cancer cell metabolism is the use of autophagy and specific forms of autophagy like mitophagy to recycle intracellular components in condition of metabolic stress or during anticancer treatments. The plasticity of cancer cell metabolism is a major limitation of anticancer treatments and could participate to therapy resistances. The aim of this review is to report recent advances in the understanding of the relationship between tumour metabolism and autophagy/mitophagy in order to propose new therapeutic strategies.
Topics: Animals; Autophagy; Cellular Reprogramming; Humans; Mitophagy; Neoplasms
PubMed: 31154012
DOI: 10.1016/j.semcdb.2019.05.029 -
Cells Apr 2022Autophagy and apoptosis represent two fundamental pathophysiological mechanisms of cell fate regulation. However, the signaling pathways of these processes are...
Autophagy and apoptosis represent two fundamental pathophysiological mechanisms of cell fate regulation. However, the signaling pathways of these processes are significantly interconnected through various mechanisms of crosstalk. Indeed, autophagy/apoptosis crosstalk is still an emerging field, in which an increasing number of molecules are involved, including, for example, PINK1 and ERLINs. On the other hand, this crosstalk involves signal transduction pathways which are strongly dependent on Ca. Interestingly, crosstalk between autophagy and apoptosis impacts several pathologies, including multiple rheumatic diseases. The purpose of this Special Issue is also to investigate the bioactive properties of drugs with antitumor activity, focusing particularly on the role of anthraquinone derivatives in the regulation of cell death and autophagy crosstalk. This Special Issue of brings together the most recent advances in understanding the various aspects of crosstalk between autophagy and apoptosis and the interconnected signaling pathways, implying therapeutic perspectives for the utility of its modulation in an anti-cancer setting.
Topics: Apoptosis; Autophagy; Humans; Neoplasms; Signal Transduction
PubMed: 35563785
DOI: 10.3390/cells11091479 -
Autophagy Mar 2023Macroautophagy (hereafter "autophagy") is a membrane-mediated biological process that involves engulfing and delivering cytoplasmic components to lysosomes for...
Macroautophagy (hereafter "autophagy") is a membrane-mediated biological process that involves engulfing and delivering cytoplasmic components to lysosomes for degradation. In addition to autophagy's pro-survival effect during nutrient starvation, excessive activation of autophagy machinery can also cause regulated cell death, especially iron-dependent ferroptosis. Here, we report a key role of TMEM164 (transmembrane protein 164) in selectively mediating ATG5 (autophagy related 5)-dependent autophagosome formation during ferroptosis, rather than during starvation. In contrast, the membrane protein ATG9A (autophagy-related 9A) is dispensable for the formation of autophagosomes during ferroptosis. TMEM164-mediated autophagy degrades ferritin, GPX4 (glutathione peroxidase 4), and lipid droplets to increase iron accumulation and lipid peroxidation, thereby promoting ferroptotic cell death. Consequently, the loss of TMEM164 limits the anticancer activity of ferroptosis-mediated cytotoxicity in mice. High TMEM164 expression is associated with improved survival and increased immune cell infiltration in patients with pancreatic cancer. These findings establish a new mode of autophagy-dependent ferroptosis.
Topics: Animals; Mice; Ferroptosis; Autophagy; Cell Death; Iron; Lysosomes
PubMed: 35947500
DOI: 10.1080/15548627.2022.2111635 -
Neurobiology of Disease Feb 2019Amyotrophic lateral sclerosis (ALS) is a debilitating and incurable disease involving the loss of motor neurons and subsequent muscle atrophy. Genetic studies have... (Review)
Review
Amyotrophic lateral sclerosis (ALS) is a debilitating and incurable disease involving the loss of motor neurons and subsequent muscle atrophy. Genetic studies have implicated deficits in autophagy and/or mitophagy in the onset of the disease. Here we review recent progress in our understanding of the pathways for autophagy and mitophagy in neurons, and how these pathways may be affected by mutations in genes including DCTN1, OPTN, TBK1, VCP, and C9ORF72. We also discuss the implications of modulating autophagy in ALS, highlighting both the potential of the approach and the concerns raised by targeting this pathway as a therapeutic strategy in neurodegenerative disease.
Topics: Amyotrophic Lateral Sclerosis; Animals; Autophagy; Humans; Mitophagy; Neurons
PubMed: 29981842
DOI: 10.1016/j.nbd.2018.07.005 -
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 -
Chinese Journal of Cancer Jun 2017Multidrug resistance (MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence. Therefore, combatting MDR is an important... (Review)
Review
Multidrug resistance (MDR) occurs frequently after long-term chemotherapy, resulting in refractory cancer and tumor recurrence. Therefore, combatting MDR is an important issue. Autophagy, a self-degradative system, universally arises during the treatment of sensitive and MDR cancer. Autophagy can be a double-edged sword for MDR tumors: it participates in the development of MDR and protects cancer cells from chemotherapeutics but can also kill MDR cancer cells in which apoptosis pathways are inactive. Autophagy induced by anticancer drugs could also activate apoptosis signaling pathways in MDR cells, facilitating MDR reversal. Therefore, research on the regulation of autophagy to combat MDR is expanding and is becoming increasingly important. We summarize advanced studies of autophagy in MDR tumors, including the variable role of autophagy in MDR cancer cells.
Topics: Antineoplastic Agents; Apoptosis; Autophagy; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Neoplasms
PubMed: 28646911
DOI: 10.1186/s40880-017-0219-2 -
Autophagy Jun 2020Macroautophagy/autophagy plays complex, context-dependent roles in cancer. How autophagy governs the emergence of metastatic disease has been incompletely understood. We...
Macroautophagy/autophagy plays complex, context-dependent roles in cancer. How autophagy governs the emergence of metastatic disease has been incompletely understood. We recently uncovered that genetic autophagy inhibition strongly attenuates primary tumor growth in mammary cancer models, yet paradoxically promotes spontaneous metastasis to the lung and enables the outgrowth of disseminated tumor cells (DTCs) into overt macro-metastases. Furthermore, at both primary and metastatic sites, genetic autophagy inhibition leads to the marked expansion of tumor cells exhibiting aggressive and pro-metastatic basal epithelial differentiation. These pro-metastatic effects of autophagy inhibition are due to the cytosolic accumulation of the autophagy cargo receptor NBR1 in autophagy-deficient tumor cells.
Topics: Autophagy; Breast Neoplasms; Carrier Proteins; Humans; Intracellular Signaling Peptides and Proteins; Macroautophagy
PubMed: 32267786
DOI: 10.1080/15548627.2020.1753001 -
Journal of Hematology & Oncology Jul 2020Both inflammasomes and autophagy have important roles in the intracellular homeostasis, inflammation, and pathology; the dysregulation of these processes is often... (Review)
Review
Both inflammasomes and autophagy have important roles in the intracellular homeostasis, inflammation, and pathology; the dysregulation of these processes is often associated with the pathogenesis of numerous cancers. In addition, they can crosstalk with each other in multifaceted ways to influence various physiological and pathological responses, including cancer. Multiple molecular mechanisms connect the autophagy pathway to inflammasome activation and, through this, may influence the outcome of pro-tumor or anti-tumor responses depending on the cancer types, microenvironment, and the disease stage. In this review, we highlight the rapidly growing literature on the various mechanisms by which autophagy interacts with the inflammasome pathway, to encourage additional applications in the context of tumors. In addition, we provide insight into the mechanisms by which pathogen modulates the autophagy-inflammasome pathway to favor the infection-induced carcinogenesis. We also explore the challenges and opportunities of using multiple small molecules/agents to target the autophagy/inflammasome axis and their effects upon cancer treatment. Finally, we discuss the emerging clinical efforts assessing the potential usefulness of targeting approaches for either autophagy or inflammasome as anti-cancer strategies, although it remains underexplored in terms of their crosstalks.
Topics: Animals; Autophagy; Clinical Trials as Topic; Homeostasis; Humans; Inflammasomes; Intracellular Membranes; Mitochondria; Mitophagy; Models, Biological; NLR Family, Pyrin Domain-Containing 3 Protein; Neoplasm Proteins; Neoplasms; RNA, Double-Stranded; RNA, Neoplasm; Reactive Oxygen Species
PubMed: 32703253
DOI: 10.1186/s13045-020-00936-9