Molecular regulation of mitophagy signaling in tumor microenvironment and its targeting for cancer therapy.

Aberrations emerging in mitochondrial homeostasis are restrained by mitophagy to control mitochondrial integrity, bioenergetics signaling, metabolism, oxidative stress, and apoptosis. The mitophagy-accompanied mitochondrial processes that occur in a dysregulated condition act as drivers for cancer occurrence. In addition, the enigmatic nature of mitophagy in cancer cells modulates the cellular proteome, creating challenges for therapeutic interventions.

The role of autophagy in Graves disease: knowns and unknowns.

Graves disease (GD), an autoimmune disease affects the thyroid gland, results in hyperthyroidisms and goiter. The main cause of GD is not clearly defined; however, stimulating autoantibodies for thyroid stimulating hormone receptor (TSHR) known as thyroid-stimulating immunoglobulins (TSIs) are the primary proposed mechanism. The TSI activation of TSHRs of thyroid gland results in excessive release of thyroid hormones with the subsequent development of hyperthyroidism and goiter.

Mammalian nucleophagy: process and function.

The nucleus is a highly specialized organelle that houses the cell's genetic material and regulates key cellular activities, including growth, metabolism, protein synthesis, and cell division. Its structure and function are tightly regulated by multiple mechanisms to ensure cellular integrity and genomic stability. Increasing evidence suggests that nucleophagy, a selective form of autophagy that targets nuclear components, plays a critical role in preserving nuclear integrity by clearing dysfunctional nuclear materials such as nuclear proteins (lamins, SIRT1, and histones), DNA-protein crosslinks, micronuclei, and chromatin fragments.

Alterations in the Processing of Platelet APP (Amyloid Beta Precursor Protein) in Alzheimer Disease: The Possible Nexus.

Alzheimer's disease (AD) is the most common neurodegenerative disease associated with the development of dementia. The hallmarks of AD neuropathology are accumulations of amyloid peptide (Aβ) and neurofibrillary tangles (NFTs). Aβ is derived from the processing of APP (amyloid beta precursor protein) by BACE1 (beta-secretase 1) and γ-secretase through an amyloidogenic pathway.

Identification of the mammalian VPS4A as a selective lipophagy receptor.

Lipophagy is a selective type of autophagy where lipid droplets are targeted to the lysosome/vacuole for degradation. Even though lipophagy has been reported in various species, many questions remain unaddressed. How are the lipid droplets sequestered to the lysosome? What is the lipophagy receptor? How is this receptor regulated at a posttranslational level? A new collaborative study among several universities conducted on mouse and human hepatocytes sheds light on these questions, deciphering the lipophagy mechanism in the liver.

The Estrogen-Autophagy Axis: Insights into Cytoprotection and Therapeutic Potential in Cancer and Infection.

Macroautophagy, commonly referred to as autophagy, is an essential cytoprotective mechanism that plays a significant role in cellular homeostasis. It has emerged as a promising target for drug development aimed at treating various cancers and infectious diseases. However, the scientific community has yet to reach a consensus on the most effective approach to manipulating autophagy, with ongoing debates about whether its inhibition or stimulation is preferable for managing these complex conditions.

The Compelling Role of Brain-Derived Neurotrophic Factor Signaling in Multiple Sclerosis: Role of BDNF Activators.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin, acting as a neurotrophic signal and neuromodulator in the central nervous system (CNS). BDNF is synthesized from its precursor proBDNF within the CNS and peripheral tissues. Through activation of NTRK2/TRKB (neurotrophic receptor tyrosine kinase 2), BDNF promotes neuronal survival, synaptic plasticity, and neuronal growth, whereas it inhibits microglial activation and the release of pro-inflammatory cytokines.

Autophagy as a way to remove DNA lesions.

Type I topoisomerases (TOP1) are critical to remove the topological stress when DNA double strands are unwound. The TOP1 cleavage complexes (TOP1cc) are normally transient, and the stabilization of TOP1cc by its inhibitors, such as camptothecin (CPT), may lead to DNA damage and become cytotoxic. The proteasome pathway degrades trapped TOP1, which is necessary for the repair machinery to gain access to the DNA; however, this process is mainly described when the CPT concentration is high, at levels which are clinically unachievable.

TgATG9 is required for autophagosome biogenesis and maintenance of chronic infection in .

is a ubiquitous protozoan parasite that can reside long-term within hosts as intracellular tissue cysts comprised of chronic stage bradyzoites. To perturb chronic infection requires a better understanding of the cellular processes that mediate parasite persistence. Macroautophagy/autophagy is a catabolic and homeostatic pathway that is required for chronic infection, although the molecular details of this process remain poorly understood.

Sex and Region-Specific Disruption of Autophagy and Mitophagy in Alzheimer's Disease: Linking Cellular Dysfunction to Cognitive Decline.

Macroautophagy and mitophagy are critical processes in Alzheimer's disease (AD), yet their links to behavioral outcomes, particularly sex-specific differences, are not fully understood. This study investigates autophagy (LC3B-II, SQSTM1) and mitophagy (BNIP3L, BNIP3, BCL2L13) markers in the cortex and hippocampus of male and female 3xTg-AD mice, using western blotting, transmission electron microscopy (TEM), and behavioral tests (novel object recognition and novel object placement). Significant sex-specific differences emerged: female 3xTg-AD mice exhibited autophagosome accumulation due to impaired degradation in the cortex, while males showed fewer autophagosomes, especially in the hippocampus, without significant degradation changes.

Minocycline Acts as a Neuroprotective Agent Against Tramadol-Induced Neurodegeneration: Behavioral and Molecular Evidence.

Background: Previous evidence indicates that tramadol (TRA) can lead to neurodegenerative events and minocycline (MIN) has neuroprotective properties.

Aim Of The Study: The current research evaluated the neuroprotective effects of MIN for TRA-promoted neurodegeneration.

Methods: Sixty adult male rats were placed into the following groups: 1 (received 0.

Preventive Effects of Crocin, a Key Carotenoid Component in Saffron, Against Nicotine-Triggered Neurodegeneration in Rat Hippocampus: Possible Role of Autophagy and Apoptosis.

Background: Nicotine is a behavioral stimulant that in high doses, through the neuro-inflammatory and oxidative stress pathway, can induce apoptosis and autophagy leading to cell death. Previous data indicate that crocin has neuroprotective properties. The aim of the current study is to investigate crocin's neuroprotective effects against nicotine-triggered neuro-inflammation, apoptosis, and autophagy in rat hippocampus.

The dual role of autophagy in suppressing and promoting hepatocellular carcinoma.

The 5-year survival rate for hepatocellular carcinoma (HCC), a deadly form of liver cancer, is quite low. Although drug therapy is successful, patients with advanced liver cancer frequently develop resistance because of the significant phenotypic and genetic heterogeneity of these cells. The overexpression of drug efflux transporters, downstream adaptive responses, malfunctioning DNA damage repair, epigenetic modification, the tumor microenvironment, and the extracellular matrix can all be linked to drug resistance.

Nuclear proteasomes as a backup for autophagy: interconnected proteostasis pathways.

Protein homeostasis (proteostasis) refers to the balance of the cellular protein environment, tightly regulated by pathways governing protein synthesis, folding, trafficking, and degradation. Growing evidence supports the interconnection of these pathways to ensure the robustness of the proteo-stasis network. A recent study by Park et al.

The interplay between probiotics and host autophagy: mechanisms of action and emerging insights.

Autophagy, a lysosome-dependent protein degradation mechanism, is a highly conserved catabolic process seen in all eukaryotes. This cell protection system, which is present in all tissues and functions at a basic level, can be up- or downregulated in response to various stresses. A disruption in the natural route of the autophagy process is frequently followed by an interruption in the inherent operation of the body's cells and organs.

Global Challenges After a Global Challenge: Lessons Learned from the COVID-19 Pandemic.

Coronavirus disease 2019 (COVID-19) has affected not only individual lives but also the world and global systems, both natural and human-made. Besides millions of deaths and environmental challenges, the rapid spread of the infection and its very high socioeconomic impact have affected healthcare, economic status and wealth, and mental health across the globe. To better appreciate the pandemic's influence, multidisciplinary and interdisciplinary approaches are needed.

Macroautophagy/autophagy promotes resistance to KRAS-targeted therapy through glutathione synthesis.

KRAS mutation-driven pancreatic ductal adenocarcinoma (PDAC) represents a major challenge in medicine due to late diagnosis and treatment resistance. Here, we report that macroautophagy (hereafter autophagy), a cellular degradation and recycling process, contributes to acquired resistance against novel KRAS-targeted therapy. The KRAS protein inhibitor MRTX1133 induces autophagy in KRAS-mutated PDAC cells by blocking MTOR activity, and increased autophagic flux prevents apoptosis.

Big1 is a newly identified autophagy regulator that is critical for a fully functional V-ATPase.

The vacuolar-type H-translocating ATPase (V-ATPase) is the major proton pump for intraorganellar acidification. Therefore, the integrity of the V-ATPase is closely associated with cellular homeostasis, and mutations in genes encoding V-ATPase components and assembly factors have been reported in certain types of diseases. For instance, the recurrent mutations of , a gene encoding a V-ATPase accessory protein, have been associated with cancers and immunodeficiency.

Why nuclease free water ruined my experiment (but at least it was free), or why the short dash matters.

There are different types of punctuation marks that are referred to as dashes. These include the short dash or hyphen (-), the en dash (-) and the em dash (-). Each of these marks has a purpose, some of which I have discussed previously.

The emerging significance of Vac8, a multi-purpose armadillo-repeat protein in yeast.

Vac8 is the sole armadillo-repeat (ARM) protein in yeast. The function of Vac8 in the cytoplasm-to-vacuole targeting pathway has been known for a long time but its role in the phagophore assembly site localization and recruitment of autophagy-related protein complexes is slowly coming to light. Because Vac8 is also involved in formation of the nuclear-vacuole junction and vacuole inheritance, the protein needs to be a competent and wide-ranging mediator of cellular processes.

Autophagy in aging-related diseases and cancer: Principles, regulatory mechanisms and therapeutic potential.

Macroautophagy/autophagy is primarily accountable for the degradation of damaged organelles and toxic macromolecules in the cells. Regarding the essential function of autophagy for preserving cellular homeostasis, changes in, or dysfunction of, autophagy flux can lead to disease development. In the current paper, the complicated function of autophagy in aging-associated pathologies and cancer is evaluated, highlighting the underlying molecular mechanisms that can affect longevity and disease pathogenesis.