…we review the correlations between autophagy and energy homeostasis in terms of oxidative phosphorylation, reactive oxygen species in mitochondria, glycolysis, metabolism of glycogen and protein, and so on. An understanding of the role of autophagy in energy homeostasis could help us better appreciate how autophagy determines cell fate under stressful conditions or pathological processes.
Energy biophysically constrains autophagy in the context of the Creation of sunlight and water, which links oxygen-dependent ecological adaptations to healthy longevity via enzyme-dependent metabolism and the physiology of reproduction in all living genera.
Lipid droplets (LDs) are the main lipid storage form in living organisms. The process of autophagic degradation of LDs is referred to lipophagy or macrolipophagy. Lipophagy is not only indispensable for the cellular lipid metabolism but also closely associated with several metabolic disorders such as obesity, hepatic steatosis, atherosclerosis, and so on.
If we add the definitions of enough terms, energy-dependent enzyme-dependent autophagy can be linked from lipophagy or macrolipophagy to mutation-driven evolution via misfolded proteins. Autophagy and the Metabolism of Misfolding Protein
…the clearance of misfolded proteins is the important function of autophagy. Impairment at different steps of the autophagy system, such as the ubiquitin-proteasome and the autophagy-lysosome pathways, may result in the accumulation of misfolded proteins in insoluble aggregates. Abnormal accumulation of misfolded proteins in cells can lead to a variety of human diseases.
The clearance of anything from anything else is energy-dependent. The wind may blow, or a broom might be used, but quantum physics cannot be linked to quantum biology without a source of energy. When viruses steal the energy required for microRNA-mediated cell type differentiation, the quality control mechanisms fail. The virus-driven degradation of messenger RNA links mutations to all pathology via perturbed mitochondrial quality control. Autophagy in Mitochondrial Quality Control
The autophagy system can selectively clear the mitochondria and other organelles, which lead to the maturation of red blood cells. Dysfunction of autophagy impairs the clearance of damaged organelles, which results in injury of cells. In the maturation of red blood cells, failure to clear the cellular organelles by autophagy will disturb the normal differentiation of red blood cells, leading to a series of diseases such as anemia.
Ingram and others found that hemoglobin S differs from A in the substitution of just a single amino acid, valine in place of glutamic acid in the beta chain of the hemoglobin molecule.
Fixation of amino acid substitutions biophyiscally constrains which intracellular components / endogenous substrates are degraded. Chaperone-Mediated Autophagy
Chaperone-mediated autophagy (CMA) was the first lysosomal process to be discovered by which intracellular components are selectively degraded. This process involves the recognition of the substrate, the unfolding and translocation of the substrate, and the degradation of the substrate.
…autophagy plays a key role in the regulation of reproduction process, and blockage of autophagy process likely contributes to reproductive abnormalities and even infertility. Here we summerize the recent progress in exploring the functional roles of autophagy in reproductive processes, such as spermatogenesis, folliculogenesis, fertilization, embryogenesis, and maternal–fetal crosstalk, in both animals and plants.
…selective overexpression of the stress protein heme oxygenase-1 (HO-1) in astrocytes of novel GFAP.HMOX1 transgenic mice results in subcortical oxidative stress and mitochondrial damage/autophagy; diminished neuronal reelin content (males); induction of Nurr1 and Pitx3 with attendant suppression of their targeting miRNAs, 145 and 133b; increased tyrosine hydroxylase and α-synuclein expression with downregulation of the targeting miR-7b of the latter; augmented dopamine and serotonin levels in basal ganglia; reduced D1 receptor binding in nucleus accumbens; axodendritic pathology and altered hippocampal cytoarchitectonics; impaired neurovascular coupling; attenuated prepulse inhibition (males); and hyperkinetic behavior.
Who decided they could disconnect the mechanistic link from alternative splicing techniques of pre-mRNA’s (Diamond, Binstock, & Kohl, 1996) to behavior by using the nomenclature associated with microRNAs, the new term for pre-mRNAs? Autophagy in Development and Differentiation
Autophagy is also important for intracellular renewal, maintaining the health of terminally differentiated cells. Studies of Drosophila, Caenorhabditis elegans, and other species revealed abnormal autophagy lead to developmental and differential abnormality, including those in salivary glands and midgut development, protein aggregation, removal of apoptotic cell corpses, and development of dauer and synapse.
Autophagy is associated with the entire life cycle of the body, from the totipotent fertilized egg to the terminally differentiated cell. However, autophagy also plays distinct roles in these different life stages and in specific cell types.
Enhanced autophagy can delay aging and prolong life span. The absence of autophagy leads to the accumulation of mutant and misfolded proteins in the cell, which is the basis for the emergence and development of neurodegenerative diseases and other aging-related diseases.
There are two main mechanisms of intracellular protein degradation: the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway (ALP). There is a certain relationship between these two mechanisms, and there are some molecules that initiate compensatory effects to prevent disease progression.
The mechanisms are energy-dependent and changes in the microRNA/messenger RNA balance have been linked to healthy longevity or from the virus-driven degradation of messenger RNA to mutations and disease progression via immune signaling and autophagy. Immune Signaling and Autophagy Regulation
…autophagy…plays a protective role against toxins, regulates cytokine production, and activates the inflammasome [and] plays an important regulatory role in thymic selection, T cell maturation, T cell polarization, T cell and B cell homeostasis, antigen processing, antigen presentation, and antibody response. On the other hand, autophagy is regulated by immunological and stress signals. The crosstalk between these signaling pathways helps maintain homeostasis and physiological functions. Dysfunction of these regulatory networks is the cause of several kinds of diseases.
Translation: Nutrient stress and social stress link failed authophagy to dysfunctional regulatory systems via virus-driven inflammation, which links mutations to all diseases via immune responses. Autophagy and the Immune Response
This review highlights the key role that autophagy plays in the innate immune system and the acquired immune system. Further clarifying the mechanism by which autophagy regulates the immune system is essential for elucidating the precise mechanisms of various diseases and for developing new treatment methods.
Translation: They know how food energy and its metabolism to species-specific pheromones regulates the immune system and protects organized genomes from the virus-driven degradation of messenger RNA, but they are not going to tell anyone that the viruses cause all diseases. Autophagy and Immune Tolerance
Numerous studies indicated that macroautophagy (hereafter named as autophagy) is involved in T cells and B cells related immune tolerance. Recently, more and more researches demonstrated that autophagy is not only capable of nonselective degradation of cellular macromolecular components but also responsible for sorting and transporting autophagic substrates through a group of cargo receptors for selective degradation, which is called as selective autophagy. Recent studies indicated that selective autophagy can effectively regulate the immune tolerance and avoid over-activation of immune response by targeting multiple receptors and effectors of immune cells.
SARCASM ALERT: 1) What’s an ‘effector’ of immune cells? 2) Why not name macroautophagy (hereafter named as autophagy) lipophagy or macrolipophagy as the authors did in Autophagy and Lipid Metabolism, and pretend that ‘effectors’ regulate immune cells? Autophagy—Cell Survival and Death
The elucidation of the regulatory role of autophagy in cell survival and death requires more research. Some research results are likely to provide hot topics for further investigations on diseases related to cell death disorders and an experimental basis for the targeted regulation of autophagy for specific treatment of diseases.
Pleas for more funding should not be made until the facts from prior research are made perfectly clear.
See: Reduced expression of brain-enriched microRNAs in glioblastomas permits targeted regulation of a cell death gene (2011)
Failed autophagy was linked to the cell death gene by researchers working for Abcam in the 1990s. The information was suppressed, but it’s becoming harder to continue doing that, especially in the context of pleas for more funding for further investigations.
Autophagy and phagocytosis orchestrate in maintaining homeostasis, in MHC class II antigen processing, in the removal of pathogens, in cell death, immunity, and inflammation. There are numerous cross talks of autophagy with biosynthetic processes such as conventional and unconventional secretion of biologically active cargo and trafficking of integral membrane proteins, as well as the exosome secretion. There are also links between autophagy and trafficking events from plasma membrane, including lateral plasma membrane proteins connexins, cell connections, and ciliogenesis.
Thanks for making that fact perfectly clear so that ages 10+ can link microRNA biogenesis to healthy longevity via autophagy and game play of: Subatomic Periodic Cytosis Virus Expansion Ecosystem
AND Genotype: After three generations, the player with the most points wins!
Everything known about the light-activated assembly of the microRNA-RNA-peptide nanocomplex links oxygen-dependent plant growth from what animals eat to biophysically constrained viral latency via autophagy.
Please see: Biological Function of Autophagy (1)
(click to enlarge)