68 Sentences With "autophagosome" | Random Sentence Generator

Then the autophagosome merges with a second vesicle known as a lysosome.

Then the autophagosome merges with a lysosome, and the lysosome's enzymes break up the autophagosome's contents.

First, the cellular components to be recycled are enclosed in a fatty membrane, to create a bubblelike vesicle called an autophagosome.

First, the cellular components to be recycled are enclosed in a fatty membrane to create another type of vesicle, an autophagosome.

This work, published in 1992, was the key to the rest—the identification of the genes involved in autophagosome assembly, and thus an understanding of how these vesicles come into being.

This work, published in 1992, was the key to the rest—the identification of the genes involved in autophagosome assembly, which in turn led to an understanding of how those vesicles come into being.

After formation of the autophagosome, the ATG12-ATG5:ATG16L complex dissociates from the autophagosome.

First the phagophore engulfs the material that needs to be degraded, which forms a double membrane known as an autophagosome, around the organelle marked for destruction. The autophagosome then travels through the cytoplasm of the cell to a lysosome, and the two organelles fuse. Within the lysosome, the contents of the autophagosome are degraded via acidic lysosomal hydrolase. Microautophagy, on the other hand, involves the direct engulfment of cytoplasmic material into the lysosome.

Autophagosome formation during chaperone-assisted selective autophagy depends on an interaction of BAG3 with SYNPO2, which triggers the cooperation with a VPS18-containing protein complex that mediates the fusion of autophagosome membrane precursors. The formed autophagosomes finally fuse with lysosomes, resulting in client degradation.

In addition to phagophore assembly, SNAREs are also important in mediating autophagosome-lysosome fusion. In mammals, the SNAREs VAMP7, VAMP8, and VTI1B are required in autophagosome-lysosome fusion and this process is impaired in lysosomal storage disorders where cholesterol accumulates in the lysosome and sequesters SNAREs in cholesterol rich regions of the membrane preventing their recycling. Recently, syntaxin 17 (STX17) was identified as an autophagosome associated SNARE that interacts with VAMP8 and SNAP29 and is required for fusion with the lysosome. STX17 is localized on the outer membrane of autophagosomes, but not phagophores or other autophagosome precursors, which prevents them from prematurely fusing with the lysosome.

EMC6 interacts with the small GTPase RAB5A and BECLIN-1, regulators of autophagosome formation. This observation suggestes that the mEMC, and not just EMC6, might be involved in regulating Rab5A and BECLIN-1. However, the molecular mechanism underlying the proposed modulation of autophagosome formation remains to be established.

The effect of Bafilomycin on autophagosome-lysosome fusion is complex and time dependent in each cell line. In neurons, an increase in the autophagosome marker LC3-II has been seen with Bafilomycin treatment. This occurs as autophagosomes fail to fuse with lysosomes, which normally stimulates the degradation of LC3-II.

Autophagy is a form of intracellular phagocytosis in which a cell actively consumes damaged organelles or misfolded proteins by encapsulating them into an autophagosome, which fuses with a lysosome to destroy the contents of the autophagosome. Because many neurodegenerative diseases show unusual protein aggregates, it is hypothesized that defects in autophagy could be a common mechanism of neurodegeneration.

The outer membrane of an autophagosome fuses with a lysosome to form an autolysosome. The lysosome's hydrolases degrade the autophagosome-delivered contents and its inner membrane. The formation of autophagosomes is regulated by genes that are well- conserved from yeast to higher eukaryotes. The nomenclature of these genes has differed from paper to paper, but it has been simplified in recent years.

The transient conjugation of Atg8 to the membrane lipid phosphatidylethanolamine is essential for phagophore expansion as its mutation leads to defects in autophagosome formation. It is distributed symmetrically on both sides of the autophagosome and it is assumed that there is a quantitative correlation between the amount of Atg8 and the vesicle size. After finishing vesicle expansion, the autophagosome is ready for fusion with the lysosome and Atg8 can either be released from the membrane for recycling (see below) or gets degraded in the autolysosome if left uncleaved. ATG8 is also required for a different autophagy-related process called the Cytoplasm- to-vacuole targeting (Cvt) pathway.

The autophagosome also fuses with lysosomes to degrade its contents. When M. tuberculosis inhibit phagosome acidification, Interferon gamma can induce autophagy and rescue the maturation process.

When galectin-8 binds to a damaged vacuole, it recruits an autophagy adaptor such as NDP52 leading to the formation of an autophagosome and bacterial degradation.

Atg3 consists of three domains, an N-terminal domain, a catalytic domain and a C-terminal domain. The catalytic domain contains a cysteine residue within an HPC motif, this is the putative active-site residue for recognition of the Apg5 subunit of the autophagosome complex. The small C-terminal domain is likely to be a distinct binding region for the stability of the autophagosome complex. It carries a highly characteristic conserved FLKF sequence motif.

After the formation of the spherical structure, the complex of ATG12-ATG5:ATG16L1 dissociates from the autophagosome. LC3 is cleaved by ATG4 protease to generate cytosolic LC3. LC3 cleavage is required for the terminal fusion of an autophagosome with its target membrane. LC3 is commonly used as a marker of autophagosomes in immunocytochemistry, because it is the essential part of the vesicle and stays associated until the last moment before its fusion.

To do this, neurons are first put into nutrient rich conditions then into nutrient starved conditions to stimulate autophagy. Bafilomycin is co- administered in the condition of nutrient stress so that while autophagy is stimulated, bafilomycin blocks its final stage of autophagosome-lysosomal fusion resulting in the accumulation of autophagosomes. Levels of autophagy related proteins associated with autophagosomes, such as LC3, can then be monitored to determine the level of autophagosome formation induced by nutrient deprivation.

The active ULK and Beclin-1 complexes re-localize to the site of autophagosome initiation, the phagophore, where they both contribute to the activation of downstream autophagy components. Once active, VPS34 phosphorylates the lipid phosphatidylinositol to generate phosphatidylinositol 3-phosphate (PtdIns(3)P) on the surface of the phagophore. The generated PtdIns(3)P is used as a docking point for proteins harboring a PtdIns(3)P binding motif. WIPI2, a PtdIns(3)P binding protein of the WIPI (WD-repeat protein interacting with phosphoinositides) protein family, was recently shown to physically bind Atg16L1.T. Proikas-Cézanne, Z. Takacs, P. Donnes, and O. Kohlbacher, 'Wipi Proteins: Essential Ptdins3p Effectors at the Nascent Autophagosome', J Cell Sci, 128 (2015), 207-17 Atg16L1 is a member of an E3-like protein complex involved in one of two ubiquitin-like conjugation systems essential for autophagosome formation.

This appears to be due to a block in the autophagosome-lysosome fusion mechanism.Hori I, Otomo T, Nakashima M, Miya F, Negishi Y, Shiraishi H, Nonoda Y, Magara S, Tohyama J, Okamoto N, Kumagai T, Shimoda K, Yukitake Y, Kajikawa D, Morio T, Hattori A, Nakagawa M, Ando N, Nishino I, Kato M, Tsunoda T, Saitsu H, Kanemura Y, Yamasaki M, Kosaki K, Matsumoto N, Yoshimori T, Saitoh S (2017) Defects in autophagosome-lysosome fusion underlie Vici syndrome, a neurodevelopmental disorder with multisystem involvement. Sci Rep 7(1):3552.

Rubinsztein has made major contributions to the field of neurodegeneration with his laboratory's discovery that autophagy regulates the levels of intracytoplasmic aggregate-prone proteins that cause many neurodegenerative diseases, including Huntington's, Parkinson's and Alzheimer's disease. His lab has found that autophagy may be inhibited in various neurodegenerative diseases and has elucidated the pathological consequences of autophagy compromise. In addition his research has advanced the basic understanding of autophagy, identifying the plasma membrane as a source of autophagosome membrane and characterising early events in autophagosome biogenesis,. Furthermore, he studied how lysosomal positioning regulates autophagy.

Gamma-aminobutyric acid A receptors [GABA(A) receptors] are ligand-gated chloride channels that mediate inhibitory neurotransmission. This gene encodes GABA(A) receptor- associated protein, which is highly positively charged in its N-terminus and shares sequence similarity with light chain-3 of microtubule-associated proteins 1A and 1B. This protein clusters neurotransmitter receptors by mediating interaction with the cytoskeleton. Moreover, GABARAP has an important function in autophagosome mediated autophagy, since it is crucial for autophagosome formation and sequestration of cytosolic cargo into double- membrane vesicles, leading to subsequent degradation after fusion with lysosomes.

This complex then activates and selectively targets p38 MAPK to the autophagosome to phosphorylate ATG5 at threonine 75. This leads to the inactivation of ATG5 and inhibition of autophagy. ATG5 can also be regulated post translationally by microRNA.

Atg1 has two distinct functions in yeast (for higher eukaryotes see below): the kinase-independent recruitment of downstream Atg proteins (i.e. PAS organization) and a kinase-dependent function in autophagosome formation likely mediated by the phosphorylation of downstream substrates.

Atg1 is a kinase upregulated upon induction of autophagy. Atg13 regulates Atg1 and together they form a complex called Atg13:Atg1, which receives signals from the master of nutrient sensing – Tor. Atg1 is also important in late stages of autophagosome formation.

An autophagosome is a spherical structure with double layer membranes. It is the key structure in macroautophagy, the intracellular degradation system for cytoplasmic contents (e.g., abnormal intracellular proteins, excess or damaged organelles, invading microorganisms). After formation, autophagosomes deliver cytoplasmic components to the lysosomes.

GRAMD1A localizes to the endoplasmic reticulum. Its GRAM domain tethers it to the plasma membrane where it can bind phosphatidylinositol phosphate in areas enriched for it. The protein alters intracellular cholesterol distribution, moving it from the plasma membrane. GRAMD1A also is necessary for autophagosome biogenesis.

Nuclear receptor coactivator 4 is a protein that in humans is encoded by the NCOA4 gene. It plays an important role in ferritinophagy, acting as a cargo receptor, binding to the ferritin heavy chain and latching on to ATG8 on the surface of the autophagosome.

Macroautophagy is a catabolic process involving the formation of double- membrane bound organelles called autophagosomes, which aid in degradation of cellular components through fusion with lysosomes. During autophagy, portions of the cytoplasm are engulfed by a cup-shaped double-membrane structure called a phagophore and eventually become the contents of the fully assembled autophagosome. Autophagosome biogenesis requires the initiation and growth of phagophores, a process that was once thought to occur through de novo addition of lipids. However, recent evidence suggests that the lipids that contribute to the growing phagophores originate from numerous sources of membrane, including endoplasmic reticulum, Golgi, plasma membrane, and mitochondria.

Microtubule-associated proteins 1A/1B light chain 3B (hereafter referred to as LC3) is a protein that in humans is encoded by the MAP1LC3B gene. LC3 is a central protein in the autophagy pathway where it functions in autophagy substrate selection and autophagosome biogenesis. LC3 is the most widely used marker of autophagosomes.

SNAREs play important roles in mediating vesicle fusion during phagophore initiation and expansion as well as autophagosome-lysosome fusion in the later stages of autophagy. Though the mechanism of phagophore initiation in mammals is unknown, SNAREs have been implicated in phagophore formation through homotypic fusion of small, clathrin-coated, single-membrane vesicles containing Atg16L, the v-SNARE VAMP7, and its partner t-SNAREs: Syntaxin-7, Syntaxin-8, and VTI1B. In yeast, the t-SNAREs Sec9p and Sso2p are required for exocytosis and promote tubulovesicular budding of Atg9 positive vesicles, which are also required for autophagosome biogenesis. Knocking out either of these SNAREs leads to accumulation of small Atg9 containing vesicles that do not fuse, therefore preventing the formation of the pre-autophagosomal structure.

AuTophaGy related 1 (Atg1) is a 101.7kDa serine/threonine kinase in S.cerevisiae, encoded by the gene ATG1. It is essential for the initial building of the autophagosome and Cvt vesicles. In a non-kinase role it is - through complex formation with Atg13 and Atg17 - directly controlled by the TOR kinase, a sensor for nutrient availability.

The pre-autophagosomal structure in yeast is described as a complex localized near the vacuole. However the significance of this localization is not known. Mature yeast autophagosomes fuse directly with vacuoles or lysosomes and do not form amphisomes as in mammals. In yeast autophagosome maturation, there are also other known players as Atg1, Atg13 and Atg17.

Sequestosome-1 is a protein that in humans is encoded by the SQSTM1 gene. Also known as the ubiquitin-binding protein p62, it is an autophagosome cargo protein that targets other proteins that bind to it for selective autophagy. By interacting with GATA4 and targeting it for degradation, it can inhibit GATA-4 associated senescence and senescence-associated secretory phenotype.

Autophagy is important for recycling cellular contents and prolonging cell life. Hanna et al. show that BNIP3 and LC3 interact to remove endoplasmic reticulum and mitochondria. When inactive BNIP3 is activated on the membrane of the mitochondria, they form homodimers where LC3 can bind to the LC3-interacting region (LIR) motif on BNIP3 and facilitates the formation of an autophagosome.

The initial step of autophagosome formation of an omegasome on the endoplasmic reticulum, followed by of elongation of structures called phagophores. The formation of autophagosomes is controlled by Atg genes through Atg12-Atg5 and LC3 complexes. The conjugate of Atg12-Atg5 also interacts with Atg16 to form larger complexes. Modification of Atg5 by Atg12 is essential for the elongation of the initial membrane.

The exact function of EVI5L is unknown. Given this, the paralogs of the gene are associated with starvation-induced autophagosome formation and trafficking and translocation of GLUT4-containing vesicles.GeneCards: TBC1 Domain Family, Member 14 TBC1 Domain Family, Member 14 FunctionGeneCards: TBC1 (Tre-2/USP6, BUB2, Cdc16) Domain Family, Member 1 BC1 (Tre-2/USP6, BUB2, Cdc16) Domain Family, Member 1 Function Therefore, EVI5L is predicted to target endocytic vesicles.

ATG7 helps these UBL proteins in targeting their molecule by binding to them and activating their transfer to an E-2 enzyme. ATG7's role in both of these autophagy-specific UBL systems makes it an essential regulator of autophagosome assembly. Homologous to the ATP-binding and catalytic sites of E1 activator proteins, ATG7 uses its cysteine residue to create a thiol-ester bond with free Ubiquitin molecules.

As a lysosomotroic drug, chloroquine typically accumulates in the lysosome disrupting their degradative function, inhibiting autophagy, and inducing apoptosis through Bax-dependent mechanisms. However, in cultured cerebellar granule neurons (CGNs) low treatment with Bafillomycin of 1 nM decreased chloroquine induced apoptosis without affecting chloroquine inhibition of autophagy. The exact mechanism of this protection is unknown, although it is hypothesized to lie downstream of autophagosome-lysosome fusion yet upstream of Bax induction of apoptosis.

The chaperone-assisted selective autophagy complex comprises the molecular chaperones HSPA8 and HSPB8, and the cochaperones BAG3 and STUB1. BAG3 facilitates the cooperation of HSPA8 and HSPB8 during the recognition of nonnative client proteins. STUB1 mediates the ubiquitination of the chaperone-bound client, which induces the recruitment of the autophagic ubiquitin adaptor SQSTM1. The adaptor simultaneously interacts with the ubiquitinated client and autophagosome membrane precursors, thereby inducing the autophagic engulfment of the client.

Fulvio Reggiori, Chao-Wen Wang, Usha Nair, Takahiro Shintani, Hagai Abeliovich, and Daniel J. Klionsky, Early Stages of the Secretory Pathway, but Not Endosomes, Are Required for Cvt Vesicle and Autophagosome Assembly in Saccharomyces cerevisiae, from Molecular Biology of the Cell Vol. 15, 2189–2204, May 2004. The organelle consists of two enclosed membranes forming an enclosed lumen, which contains cytoplasm. It is formed by vesicles budding off the Golgi apparatus or the endoplasmic reticulum.

Nutrient dependent autophagy is only fully inhibited if both ULK1 and ULK2 are knocked out. ULK1 has many downstream phosphorylation targets to aid in this induction of the isolation membrane/ autophagosome. Recently, a mechanism for autophagy has been elucidated. Models have proposed that the active ULK1 directly phosphorylates Beclin-1 at Ser 14 and activates the pro-autophagy class III phosphoinositide 3-kinase (PI(3)K), VPS34 complex, to promote autophagy induction and maturation.

There are specific receptor proteins that recruit items to the phagophore. The phagophore expands to accommodate the items, until the omegasome is closed to produce the roughly spherical autophagosome. How autophagosomes are "detached" or "exit" from the omegasome is not clear, but autophagocytosis associated protein Atg3 and other proteins are required, and collections of thin tubules at the junction between omegasome and phagophore appear to be involved. Actin is also believed to be important.

LC3-I is conjugated to phosphatidylethanolamine (PE) also in a ubiquitin-like reaction that requires Atg7 and Atg3. The lipidated form of LC3, known as LC3-II, is attached to the autophagosome membrane. Autophagy and apoptosis are connected both positively and negatively, and extensive crosstalk exists between the two. During nutrient deficiency, autophagy functions as a pro-survival mechanism, however, excessive autophagy may lead to cell death, a process morphologically distinct from apoptosis.

Common feature of cTECs and mTECs is constitutive macroautophagy. This process involves engulfment of portion of cytoplasm that contains organelles and vesicles into autophagosome that fuses with late endosomes or lysosomes and its content is chopped to small peptides. cTECs and mTECs utilize this endogenous pathway for MHC II presentation during selection processes, instead of common loading of exogenous peptides. Mouse with deficient macroautophagy, specifically in the thymus, revealed reduced numbers and repertoire of CD4 T cells.

In a study using 164 tumor samples from patients with diffuse large B cell lymphoma, TMEM39B was one of 17 genes identified as part of a prognostic profile for 5-year progression- free survival. In another study using a genome-wide siRNA screen, knockdown of TMEM39B with siRNAs decreased viral capsid/autophagosome colocalization, survival of virus-infected cells, and mitophagy in HeLa cells infected with Sindbis virus. This may suggest that TMEM39B plays a role in viral autophagy like its paralog TMEM39A.

Atg1 can associate with a number of other proteins of the Atg family to form a complex that functions in autophagosome or Cvt vesicle formation. The initiation of autophagy involves the building of the pre-autophagosomal structure (PAS). Most Atg proteins accumulate at the PAS and generate either Cvt vesicles under normal growing conditions or autophagosomes under starvation. To date, there are 31 ATG genes, which can be classified into several different groups according to their functions at the different steps of the pathway.

These types of membranes differ in lipid and protein composition. Distinct types of membranes also create intracellular organelles: endosome; smooth and rough endoplasmic reticulum; sarcoplasmic reticulum; Golgi apparatus; lysosome; mitochondrion (inner and outer membranes); nucleus (inner and outer membranes); peroxisome; vacuole; cytoplasmic granules; cell vesicles (phagosome, autophagosome, clathrin-coated vesicles, COPI-coated and COPII- coated vesicles) and secretory vesicles (including synaptosome, acrosomes, melanosomes, and chromaffin granules). Different types of biological membranes have diverse lipid and protein compositions. The content of membranes defines their physical and biological properties.

RalA is one of two proteins in the Ral family, which is itself a subfamily within the Ras family of small GTPases. As a Ras GTPase, RalA functions as a molecular switch that becomes active when bound to GTP and inactive when bound to GDP. RalA can be activated by RalGEFs and, in turn, activate effectors in signal transduction pathways leading to biological outcomes. For instance, RalA interacts with two components of the exocyst, Exo84 and Sec5, to promote autophagosome assembly, secretory vesicle trafficking, and tethering.

RalB is one of two proteins in the Ral family, which is itself a subfamily within the Ras family of small GTPases. As a Ras GTPase, RalB functions as a molecular switch that becomes active when bound to GTP and inactive when bound to GDP. RalB can be activated by RalGEFs and, in turn, activate effectors in signal transduction pathways leading to biological outcomes. For instance, RalB interacts with two components of the exocyst, Exo84 and Sec5, to promote autophagosome assembly, secretory vesicle trafficking, and tethering.

By electron microscopy, they saw a blockage of autophagosome-lysosome fusion after using bafilomycin at a concentration of 100 nM for 1 hour. This has been confirmed by other studies, particularly two that found decreased colocalization of mitochondria and lysosomes by fluorescence microscopy following a 12-24 hour treatment with 100 or 400 nM Bafilomycin. However, further studies have failed to see this inhibition of fusion with similar bafilomycin treatments. These contradictory results have been explained by time differences among treatments as well as use of different cell lines.

During selective autophagy, cargo is specifically targeted for degradation, and distinct cargo receptors have been described that regulate selectivity. This process is facilitated by autophagy receptors specifically recognizing and binding their cargo, and delivering it to the phagophore. In humans, there are six different LC3/GABARAP proteins, which play a central role by connecting nascent autophagosome membranes and cargo-loaded autophagy receptors to facilitate engulfment, sometimes mediated or supported by additional adaptor proteins . CEF scientists showed that GABARAP proteins are not only involved in autophagy but also in the ubiquitin-dependent degradation of TIAM1 .

After starvation autophagy is induced through the activation of Atg proteins both on the protein modification and the transcriptional level. Atg8 is especially important in macroautophagy which is one of three distinct types of autophagy characterized by the formation of double-membrane enclosed vesicles that sequester portions of the cytosol, the so-called autophagosomes. The outer membrane of these autophagosomes subsequently fuses with the lysosome/vacuole to release an inter single membrane (autophagic body) destined for degradation. During this process, Atg8 is particularly crucial for autophagosome maturation (lipidation).

Like most Atg proteins, Atg8 is localized in the cytoplasm and at the PAS under nutrient-rich conditions, but becomes membrane-associated in case of autophagy induction. It then localizes to the site of autophagosome nucleation, the phagophore-assembly site (PAS). Nucleation of the phagophore requires the accumulation of a set of Atg proteins and of class III phosphoinositide 3-kinase complexes on the PAS. The subsequent recruitment of Atg8 and other autophagy-related proteins is believed to trigger vesicle expansion in a concerted manner, presumably by providing the driving force for membrane curvature.

Many ARM-containing proteins (ARM-CPs) are also involved in autophagosome formation and maturation and a few of them in regulating signaling pathways. Autophagy Receptor Motif Plotter assists in the identification of novel ARM-CPs. Users input a given an amino acid sequence into the web-enabled tool, and the program identifies internal sequences matching a pattern within the 3 classes of the extended ARM motif (x6-W/F/Yxxx-x2). The program then computes and lists the top four scores for each motif class (W-, F-, Y-).

Vesicular stomatitis virus is believed to be taken up by the autophagosome from the cytosol and translocated to the endosomes where detection takes place by a pattern recognition receptor called toll-like receptor 7, detecting single stranded RNA. Following activation of the toll- like receptor, intracellular signaling cascades are initiated, leading to induction of interferon and other antiviral cytokines. A subset of viruses and bacteria subvert the autophagic pathway to promote their own replication. Galectin-8 has recently been identified as an intracellular "danger receptor", able to initiate autophagy against intracellular pathogens.

The subcellular localization of STING has been elucidated as an endoplasmic reticulum protein. Also, it is likely that STING associates in close proximity with mitochondria associated ER membrane (MAM)-the interface between the mitochondrion and the ER. During intracellular infection, STING is able to relocalize from endoplasmic reticulum to perinuclear vesicles potentially involved in exocyst mediated transport. STING has also been shown to colocalize with autophagy proteins, microtubule- associated protein 1 light chain 3 (LC3) and autophagy-related protein 9A, after double-stranded DNA stimulation, suggesting its presence in the autophagosome.

WIPI2 mRNA is readily detectable in several commonly used laboratory cell lines (HEK293A, HeLa, A431) and several cancer cell lines, while WIPI1 expression is limited to cancer cells. The Atg proteins regulate autophagy, which is a lysosomal degradation pathway required for maintaining cell health, surviving periods of nutrient deprivation and also plays a role in cancer, neurodegeneration and immune responses to a diverse range of pathogens. WIPI2 is recruited early to the forming autophagosome, along with DFCP-1, ULK-1 and Atg16, where it positively regulates the lipidation of Atg8 (LC3). This is not true for WIPI1.

It appears that only after extraction from the membranes or large protein assembly like ribosome, can polypeptides be degraded by the proteasome. In addition to this ‘segregase’ function, p97/CDC48 might have an additional role in shuttling the released polypeptides to the proteasome. This chaperoning function seems to be particularly important for degradation of certain aggregation-prone misfolded proteins in nucleus. Several lines of evidence also implicate p97 in autophagy, a process that turns over cellular proteins (including misfolded ones) by engulfing them into double-membrane- surrounded vesicles named autophagosome, but the precise role of p97 in this process is unclear.

Atg8 is one of the key molecular components involved in autophagy, the cellular process mediating the lysosome/vacuole-dependent turnover of macromolecules and organelles. Autophagy is induced upon nutrient depletion or rapamycin treatment and leads to the response of more than 30 autophagy-related (ATG) genes known so far, including ATG8. How exactly ATG proteins are regulated is still under investigation, but it is clear that all signals reporting on the availability of carbon and nitrogen sources converge on the TOR signalling pathway and that ATG proteins are downstream effectors of this pathway. In case nutrient supplies are sufficient, the TOR signaling pathway hyperphosphorylates certain Atg proteins, thereby inhibiting autophagosome formation.

Newly synthesized LC3's C-terminus is hydrolyzed by a cysteine protease called ATG4B exposing Gly120, termed LC3-I. LC3-I, through a series of ubiquitin-like reactions involving enzymes ATG7, ATG3, and ATG12-ATG5-ATG16, becomes conjugated to the head group of the lipid phosphatidylethanolamine. The lipid modified form of LC3, referred to as LC3-II, is believed to be involved in autophagosome membrane expansion and fusion events. However, the exact role of LC3 in the autophagic pathway is still discussed, and the question of whether LC3 is required for autophagy is debated since knockdown of MAP1LC3B is compensated by the other members of the MAP1LC3 subfamily.

Ulk1/2 is an important protein in autophagy for mammalian cells, and is homologous to ATG1 in yeast. It is part of the ULK1-complex, which is needed in early steps of autophagosome biogenesis. The ULK1 complex also consists of the FAK family kinase interacting protein of 200 kDa (FIP200 or RB1CC1) and the HORMA (Hop/Rev7/Mad2) domain-containing proteins ATG13 and ATG101. ULK1, specifically, appears to be the most essential for autophagy and is activated under conditions of nutrient deprivation by several upstream signals which is followed by the initiation of autophagy. However, ULK1 and ULK2 show high functional redundancy; studies have shown that ULK2 can compensate for the loss of ULK1.

A critical regulator of autophagy induction is the kinase mTOR, which when activated, suppresses autophagy and when not activated promotes it. Three related serine/threonine kinases, UNC-51-like kinase -1, -2, and -3 (ULK1, ULK2, UKL3), which play a similar role as the yeast Atg1, act downstream of the mTOR complex. ULK1 and ULK2 form a large complex with the mammalian homolog of an autophagy-related (Atg) gene product (mAtg13) and the scaffold protein FIP200. Class III PI3K complex, containing hVps34, Beclin-1, p150 and Atg14-like protein or ultraviolet irradiation resistance-associated gene (UVRAG), is required for the induction of autophagy. The ATG genes control the autophagosome formation through ATG12-ATG5 and LC3-II (ATG8-II) complexes.

This complex binds and activates Atg3, which covalently attaches mammalian homologues of the ubiquitin-like yeast protein ATG8 (LC3A-C, GATE16, and GABARAPL1-3), the most studied being LC3 proteins, to the lipid phosphatidylethanolamine (PE) on the surface of autophagosomes. Lipidated LC3 contributes to the closure of autophagosomes, and enables the docking of specific cargos and adaptor proteins such as Sequestosome-1/p62. The completed autophagosome then fuses with a lysosome through the actions of multiple proteins, including SNAREs and UVRAG. Following the fusion LC3 is retained on the vesicle's inner side and degraded along with the cargo, while the LC3 molecules attached to the outer side are cleaved off by Atg4 and recycled.

Galectin-8 has recently been shown to have a role in cellular defence, against both bacterial cytosolic infection and vacuolar damage. Many intracellular bacteria, such as S. enterica serovar Typhimurium and S. flexneri prefer to replicate inside and outside of the vacuole safety respectively, yet these vacuoles may become damaged, exposing bacteria to the host cell cytoplasm. It has been shown that the binding of galectin-8 to the damaged vacuole can recruit autophagy adaptors such as NDP52 leading to the formation of an autophagosome and subsequent bacterial destruction. As knockout experiments of galectin-8 leads to more successful cytosolic replication by S. enterica serovar Typhimurium, it is thought that galectin-8 acts as a danger receptor in defence against intracellular pathogens.

Defects in autophagy have been linked to various human diseases, including neurodegeneration and cancer, and interest in modulating autophagy as a potential treatment for these diseases has grown rapidly. Three forms of autophagy are commonly described: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). In macroautophagy, cytoplasmic components (like mitochondria) are targeted and isolated from the rest of the cell within a double-membraned vesicle known as an autophagosome, which, in time, fuses with an available lysosome, bringing its specialty process of waste management and disposal; and eventually the contents of the vesicle (now called an autolysosome) are degraded and recycled. In disease, autophagy has been seen as an adaptive response to stress, promoting survival of the cell; but in other cases it appears to promote cell death and morbidity.