Search Results (1,050)

Malignant mesothelioma is an aggressive cancer with limited therapeutic options, highlighting the need for novel strategies targeting metabolic vulnerabilities. Natural polyphenols have gained attention due to their ability to modulate cellular metabolism and apoptosis-related signaling pathways. In this study, we investigated the combined anticancer effects of quercetin (QUE) and arctigenin (ATG) in human malignant mesothelioma cells. QUE and ATG reduced the viability of MSTO-211H cells in a time-dependent manner, while non-malignant mesothelial MeT-5A cells showed relatively limited sensitivity under the tested conditions. Compared with single treatment, the combination treatment further enhanced growth inhibition, with combination index analysis suggesting a potential synergistic interaction. Co-treatment significantly decreased intracellular ATP levels and increased caspase-3/7 activity, suggesting metabolic stress-associated apoptotic responses. Annexin V analysis confirmed increased apoptotic cell populations following combination treatment. Western blot analysis demonstrated reduced expression of anti-apoptotic proteins Mcl-1 and Bcl-xL, along with increased cleavage of caspase-3 and PARP, consistent with involvement of intrinsic apoptosis-associated signaling pathways. In addition, increased phosphorylation of AMPK and altered expression of mitochondrial oxidative phosphorylation (OXPHOS) complex proteins were associated with potential alterations in mitochondrial respiratory protein expression. Collectively, these findings suggest that QUE and ATG co-treatment is associated with increased apoptotic cell death in malignant mesothelioma cells in association with metabolic stress–related mitochondrial functional alterations. Full article

Cadmium (Cd) is a pervasive environmental contaminant with potent cytotoxic effects in a wide range of organisms. Although autophagy and apoptosis are recognized as major cellular responses to heavy metal stress, the molecular basis of Cd-induced cell death in insects remains insufficiently understood. In this study, we used fifth-instar day-4 (5L4D) larvae of Bombyx mori and the silkworm-derived Bm-12 cell line to investigate the involvement of three core autophagy-related proteins, Bombyx mori Autophagy-related protein 5(BmATG5), Bombyx mori Autophagy-related protein 6(BmATG6), and Autophagy-related protein 8(BmATG8), in Cd-induced autophagy and apoptosis. Exposure to CdCl₂ markedly induced autophagic and apoptotic responses in both larval midgut tissue and Bm-12 cells, as demonstrated by monodansylcadaverine(MDC) staining, Lyso-Tracker Red staining, DAPI and Hoechst 33258 staining, and DNA fragmentation assays. qPCR and Western blot analyses showed significant upregulation of BmATG5, BmATG6, and BmATG8 following Cd exposure. Notably, the cleaved forms tBmATG5-N (24 kDa) and tBmATG6-C (35 and 37 kDa), as well as the lipidated form BmATG8-PE (12 kDa), accumulated substantially under Cd stress. In parallel, intracellular Ca²⁺ levels and calpain activity were significantly increased, suggesting activation of a calcium-dependent regulatory pathway. Pharmacological inhibition experiments further indicated that autophagy and apoptosis are functionally interconnected during the Cd response. Collectively, these findings demonstrate that BmATG5, BmATG6, and BmATG8, together with their processed forms, play central roles in coordinating autophagy–apoptosis crosstalk during Cd-induced cytotoxicity in Bombyx mori. This study provides new mechanistic insight into heavy metal toxicity in insects and expands our understanding of stress-induced programmed cell death during silkworm metamorphosis. Full article

Autophagy is a conserved degradation pathway essential for cellular homeostasis in plants. Selective autophagy confers cargo specificity through receptors, among which NEIGHBOR OF BRCA1 GENE1 (NBR1) is one of the best-characterized. NBR1 mediates the selective turnover of ubiquitinated or stress-damaged cargoes, including protein aggregates and damaged organelles, by linking them to ATG8-decorated autophagosomes via its AIM and UBA domains. This process supports proteostasis, plant development, and adaptation to abiotic stresses, including heat, drought, chilling, salinity, and heavy metals, as well as biotic stresses from bacteria, fungi, viruses, and oomycetes. In this review, we summarize current advances in understanding NBR1 structure, evolutionary conservation, and cargo recognition mechanisms, and highlight its interplay with phytohormone signaling and the ubiquitin–proteasome system (UPS) in shaping plant growth and stress resilience. Full article

Background/Objectives: Bladder cancer treatment is frequently hindered by chemoresistance to agents such as cisplatin, a process in which autophagy is hypothesized to play a cytoprotective role. This study aimed to investigate the time-dependent transcriptional dynamics of autophagy-related genes in response to cisplatin in bladder cancer cell lines to better elucidate the molecular underpinnings of this resistance. Methods: Two human bladder cancer cell lines, T24 and 5637, were exposed to varying concentrations of cisplatin. Cell viability and half-maximal inhibitory concentration (IC₅₀) values were determined at 24 and 48 h using the MTS assay. Subsequently, the relative mRNA expression levels of key autophagy-related genes (ULK1, BECN1, ATG5, ATG7, LC3B, SQSTM1/p62, LAMP1, and TFEB) were quantitatively analyzed via RT-qPCR at 0, 6, 24, and 48 h intervals. Results: Cisplatin exerted a dose- and time-dependent cytotoxic effect, with 5637 cells exhibiting significantly greater sensitivity compared to T24 cells. Transcriptional analysis revealed a dynamic, multiphasic modulation of the autophagic pathway: an early-phase upregulation of initiation genes (ULK1, BECN1), a mid-phase increase in autophagosome formation genes (ATG5, ATG7), and a late-phase alteration in lysosomal regulation genes (LAMP1, TFEB). Notably, the more chemoresistant T24 cells mounted a robust and sustained autophagic transcriptional response, whereas the sensitive 5637 cells demonstrated a more limited and transient reaction. Conclusions: Cisplatin modulates the autophagic pathway at the transcriptional level in a highly dynamic, time-dependent, and cell-line-specific manner. Interpreted alongside established functional evidence in the literature, the sustained autophagic gene expression observed in the resistant cells is consistent with a potential cytoprotective role, warranting further functional validation at the protein level. These findings map the temporal genetic landscape of cisplatin-induced autophagy, providing a theoretical framework for optimizing the timing of autophagy-targeted combination therapies in bladder cancer. Full article

Oxidative stress is one of the major environmental stresses that the fungal pathogen Candida albicans frequently encounters. In view of the negative regulatory effect of Ume6 on autophagy in Saccharomyces cerevisiae and the close link between autophagy and oxidative stress in mammals, we explored the regulatory effect of Ume6 on autophagy and oxidative stress in C. albicans in this study. Here, we identify the transcriptional regulator Ume6 as a key positive regulator of autophagy under oxidative stress conditions. Deletion of UME6 resulted in reduced autophagy levels under H₂O₂ treatment, correlating with reduced transcriptional expression of core autophagy-related genes. Although UME6 deletion alone did not alter H₂O₂ sensitivity, it significantly exacerbated the sensitivity of a catalase mutant, revealing a functional role for Ume6 in oxidative stress tolerance. Intriguingly, we discovered that 3-methyladenine (3-MA), a canonical autophagy inhibitor in other systems, acts as an autophagy activator in C. albicans, promoting Atg8 transport to the vacuole and enhancing autophagy levels. This 3-MA-induced autophagy alleviated oxidative stress damage, as evidenced by improved growth and protection of vacuolar membrane integrity in H₂O₂-treated cells. Furthermore, deletion of UME6 or nitrogen starvation reduced apoptosis under oxidative stress, including decreased Annexin-V binding, metacaspase activation, mitochondrial membrane depolarization, and mitochondrial cytochrome c release. This study uncovers the critical role of Ume6 in governing oxidative stress, autophagy, and apoptosis. Full article

Cadmium (Cd), a common environmental and occupational toxicant, is an important risk factor for neurodegenerative diseases. Metformin has been found to have neuroprotective effect, in addition to antidiabetic function. Our recent studies have identified that metformin ameliorates Cd neurotoxicity via blocking ROS-dependent PP5/AMPK-JNK signaling pathway. Here we further show that metformin protected PC12 cells and primary neurons from Cd-poisoning by mitigating Cd-induced increases in ATG5/LC3-II/p62 levels and autophagosomes. Knockdown of ATG5 dramatically potentiated the inhibitory effects of metformin on Cd-induced LC3-II, cleavage of caspase-3, accumulation of autophagosomes and apoptosis in PC12 cells. Addition of chloroquine (CQ) strengthened the basic and Cd-elevated ATG5/LC3-II/p62 levels, autophagosome accumulation and cell apoptosis, whereas metformin powerfully blocked the events, implying a metformin-promoted autophagic flux-dependent mechanism involved. Further research revealed that metformin prevented Cd-induced autophagic flux impairment and cell apoptosis, which was attributed to restraining Cd inactivation of AMPK. This is supported by the findings that activation of AMPK with AICAR or ectopic expression of constitutively active AMPKα (AMPKα-ca) reinforced the inhibitory effects of metformin on Cd-evoked ATG5/LC3-II/p62/autophagosomes and apoptosis in PC12 cells and/or primary neurons. Taken together, the results indicate that metformin protects neuronal cells from Cd-induced autophagic flux impairment-dependent apoptosis by activating AMPK. Our studies highlight that metformin has a great potential for prevention of Cd toxicity related to neurodegenerative diseases. Full article

High ammonia nitrogen stress significantly compromises the survival of Litopenaeus vannamei under low-salinity conditions. However, existing studies predominantly focus on ammonia nitrogen responses under single stressors or normal seawater salinity. The molecular regulatory mechanisms, metabolic remodeling patterns, and key pathway interactions in shrimp subjected to high ammonia nitrogen stress under low-salinity environment remain unclear. In this study, we employed integrated transcriptomic and metabolomic analyses to unveil the underlying molecular responses and metabolic biomarkers in the gills of L. vannamei to ammonia stress under low-salinity conditions. First, L. vannamei underwent low-salinity acclimation from 30‰ to 5‰ salinity and was then reared for one week to acclimate to the experimental environment. Subsequently, shrimp were treated with 42.32 mg/L ammonia nitrogen for a consecutive 96 h period. Integrated transcriptomic and metabolomic analyses elucidated the stress response patterns in the gills of L. vannamei under low-salinity ammonia nitrogen exposure. Specifically, 352, 802, and 140 differentially expressed genes (DEGs) were identified at 12 h, 48 h, and 96 h post-exposure, respectively. GO and KEGG enrichment analyses revealed that the significant DEGs were primarily enriched in six major pathways: autophagy, immune-related pathway, ABC transporter, fatty acid degradation and metabolism, metabolic pathway, and PPAR signaling pathway. Metabolomic profiling identified numerous differentially accumulated metabolites (DAMs) in both positive and negative ion modes, with significantly altered DAMs mainly consisting of organic acids and their derivatives, phospholipids, and other related metabolites. Key DAMs included taurine, guanosine, 1-palmitoyl-sn-glycero-3-phosphocholine, pseudouridine, and betaine. Integrative multi-omics analysis revealed that L. vannamei mediates stress responses by modulating five core pathways under low-salinity/high-ammonia-nitrogen dual stress: fatty acid degradation and metabolism (e.g., acyl-CoA dehydrogenase short chain (Acads), acetyl-CoA acetyltransferase 2 (ACAT2)), autophagy (e.g., autophagy-related protein 101-like (atg101)), immune regulation pathway (e.g., V-type proton ATPase subunit H-like (VhaSFD), actin-5C-like (Act5C)), metabolic pathway (e.g., molybdopterin synthase catalytic subunit-like (Mocs2B), cytochrome P450 2U1-like (Cyp2b1)), and ABC transporter (e.g., ATP-binding cassette sub-family D member 3-like (ABCD3), ATP-binding cassette sub-family B member 10 (ABCB10)). Through characterization of these core pathways, this study reveals the fundamental mechanisms by which L. vannamei responds to high ammonia nitrogen stress following low-salinity acclimation, providing a theoretical foundation for estuarine shrimp farming. Full article

Background: The aim of this study is to investigate the relationship between the expression levels of autophagy-related genes (SQSTM1, Beclin1, Atg5, and Atg7) in diffuse astrocytic tumors and clinicopathological parameters, including tumor grade, IDH mutation status, and survival outcomes. Materials and Methods: A total of 150 histopathologically confirmed diffuse astrocytic tumor cases were retrospectively analyzed. Clinical data were extracted from patient records. Gene expression levels were determined using qRT-PCR and evaluated by the 2^−ΔCt method, where lower ΔCt values indicate higher gene expression. IDH1 R132H mutation status was evaluated by immunohistochemistry. Results: No statistically significant differences were observed in the expression levels of SQSTM1, Beclin1, Atg5, and Atg7 across WHO tumor grades (p > 0.05). However, when analyzed by IDH status, IDH-mutant tumors exhibited significantly higher gene expression levels (demonstrated by lower ΔCt values) of Beclin1 (p = 0.046) and Atg5 (p = 0.027) compared to IDH wild-type tumors. In multivariate Cox regression analysis, age and WHO tumor grades were confirmed as independent prognostic factors. Crucially, higher SQSTM1 expression independently predicted worse clinical outcomes, specifically poorer overall survival (OS) (p = 0.004) and shorter progression-free survival (PFS) (p = 0.031). Additionally, elevated Beclin1 expression was identified as an independent predictor of worse OS (p = 0.023). Conclusions: This study demonstrates that increased expression of autophagy-related genes, particularly SQSTM1 and Beclin1, serves as a robust indicator of poor prognosis and shorter survival times in diffuse astrocytic tumors. Furthermore, the elevated expression of Beclin1 and Atg5 in IDH-mutant cases highlights a complex metabolic interplay that warrants further investigation as potential therapeutic targets. Full article

The autophagy regulator ATG7 helps maintain cellular homeostasis and has been suggested to modulate aspects of antiviral immune responses. In Drosophila, ATG7-dependent autophagy contributes to host resistance to vesicular stomatitis virus (VSV), a negative-strand RNA virus of family Rhabdoviridae that is widely used for studying viral biology and developing vaccines and virotherapy. However, the role of ATG7 in mammalian cells, especially non-immune cell types, remains unclear. Herein, we systematically examined the impact of ATG7 on VSV infection using CRISPR-edited cell lines derived from murine embryonic fibroblast (MEF), HeLa, and Huh7.5 cells, in relation to its effect on the expression of antiviral interferon-stimulated genes (ISGs). We found that ATG7 deficiency blocked basal as well as VSV-induced LC3B lipidation, concomitant with moderate reductions in progeny virus yields, while the reconstitution of ATG7 reversed the phenotypes. Mechanistically, ATG7 did not affect viral entry but rather was associated with moderate upregulation of VSV RNA replication. Intriguingly, ATG7 inhibited baseline ISG expression, and this correlated with its pro-VSV effect in all three cell types, while its suppression of innate immune responses elicited post-VSV infection did not. Altogether, these data provide new insights into the role of ATG7 in regulating VSV replication and innate immunity and have implications for developing VSV-based prophylaxis/therapeutics. Full article

Background: Kölliker’s organ (KO) support cells undergo orderly, time-dependent degeneration that is essential for auditory development and is accompanied by precisely regulated autophagic activity; however, the molecular hierarchy linking autophagy to this remodeling remains obscure. This study aimed to elucidate the regulatory mechanisms connecting autophagic flux to lysosomal biogenesis and auditory function during cochlear development. Method: We established an Atg5^flox/flox; Sox2Cre+ mouse model with deletion of the autophagy gene Atg5 in cochlear-supporting cells. Auditory function was assessed via Auditory Brainstem Response (ABR) testing. Transcriptomic profiling of the neonatal basilar membrane was performed to screen for downstream targets. Mechanistic validation included spatiotemporal immunofluorescence mapping (E18–P30) and in vitro functional assays using siRNA-mediated knockdown and lysosomal tracking. Results: At 2 months of age, Atg5^flox/flox; Sox2Cre+ mice exhibited moderate-to-severe sensorineural hearing loss accompanied by significant outer hair cell loss. Bulk RNA-seq of the basilar membrane identified fork-head box A3 (Foxa3) as a significantly downregulated transcription factor within the lysosomal–autophagy network. Spatiotemporal immunolabelling from embryonic day 18 to postnatal day 30 revealed that FOXA3 expression becomes progressively restricted to KO cells during postnatal development, with ATG5 loss reducing FOXA3 protein levels by 62.4%. In vitro, deficiency of either Atg5 or Foxa3 in primary KO cells resulted in comparable reductions in LAMP1-positive puncta. Conclusions: These findings support a model wherein the ATG5-FOXA3 axis contributes to lysosomal biogenesis in developing KO cells, with implications for understanding mechanisms of congenital sensorineural hearing loss. Full article

The fungal pathogen Candida albicans coordinated metabolism, organelle homeostasis, and stress responses for adapting to diverse host environments and maintaining virulence. While transcriptional control of these processes has been extensively studied, the contribution of post-transcriptional regulation remains incompletely understood. Here, we identify the P-body component Lsm1 as a critical factor of metabolic adaptation, mitochondrial homeostasis, and pathogenicity in C. albicans. Transcriptomic analysis revealed that loss of Lsm1 causes global transcriptional imbalance, leading to dysfunction of amino acid metabolism, mitochondrial function, endocytic trafficking, and autophagy processes. This dysfunction is accompanied by diminished TORC1 activity. Due to the aberrant TORC1 regulation caused by loss of Lsm1, ATG mRNA stability and autophagy flux was impaired under nutrient-rich condition and nitrogen starvation condition. In this context, the lsm1Δ/Δ cells established an adaptive metabolic and redox state characterized by altered NAD⁺/NADH and NADP⁺/NADPH balance, and enhanced antioxidant capacity. Moreover, the lsm1Δ/Δ cells displayed the defects in hyphal development, biofilm formation, and host cell interaction, and exhibited the attenuated virulence in a murine infection model. Together, our findings revealed that Lsm1-mediated post-transcriptional regulation is associated with the maintenance of amino acid metabolism, mitochondrial function, and TORC1 activity to fungal virulence, revealing a potential therapeutic target for C. albicans infections. Full article

Autophagy-mitophagy pathways are essential for regulating immune homeostasis. However, their contribution to population-level chronic low-grade systemic inflammation (SI) remains unclear. The objective was to investigate the association between variation in the genes related to the autophagy-mitophagy pathways and SI, and to examine whether lifestyle factors modify this relationship. We conducted genome-wide association studies and gene-set enrichment analyses using data from the Korean Genome and Epidemiology Study (KoGES, n = 28,102) and UK Biobank (UKBB, n = 343,892). SI was defined as an elevated white blood cell count or high-sensitivity C-reactive protein. Using Core Longevity State Vectors (CLSVs)—gene sets representing immune-longevity pathways derived from comparative transcriptomic analysis—we tested six pathways and constructed a weighted genetic risk score (GRS) from significant variants. Gene–lifestyle interactions were examined with respect to major dietary and lifestyle factors. Among six CLSVs, only CLSV-2 (mitophagy and autophagy) showed a significant association with SI (β = 0.425, p = 0.008). Six single nucleotide polymorphisms (SNPs) in autophagy-mitophagy genes (INPP5D, ATG16L1, ATG7, AP3S1, OPTN, and VPS33A) were associated with SI in KoGES (p < 5 × 10⁻⁵), and ten SNPs (genes selected in KoGES plus RAB7A, ATG12, VPS33A, BECN1) reached genome-wide significance in UKBB (p < 5 × 10⁻⁸). A higher GRS was associated with increased SI in both cohorts and was strongly associated with metabolic syndrome (MetS, OR = 1.91 in KoGES; OR = 1.62 in UKBB). SI was characterized by neutrophilia with relative lymphopenia. In UKBB, significant gene–lifestyle interactions were observed for diet, physical activity, smoking, and alcohol (p < 0.01). Favorable lifestyle factors reduced SI most effectively in individuals with protective genotypes. Among individuals with a high vegetable/fruit intake, SI prevalence was 35%, 36%, and 38% in the negative-, zero-, and positive-GRS groups, respectively, compared with 36%, 45%, and 48% in the low-intake groups. In conclusion, genetic variations in autophagy-mitophagy pathways specifically influence SI. Genetic predisposition substantially modifies the benefits of lifestyle, underscoring the importance of integrating genetic and lifestyle factors in understanding SI susceptibility. Full article

Bellamya limnophila is a mollusk of significant medical and economic value in China. Understanding the complete mitochondrial genome of this species will better establish a foundation for systematic classification research on Viviparidae. Therefore, we sequenced the complete mitochondrial genome of B. limnophila, conducted a comprehensive analysis of its structural characteristics, and constructed a phylogenetic tree using maximum likelihood and Bayesian methods. The results showed that the genome sequence is 16,991 bp in length, including 13 protein-coding genes (PCGs), 20 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and 1 non-coding region (D-loop). In summary, the Ka/Ks ratios of all PCGs were <1, indicating that purifying selection dominated the evolutionary process of these snails. The entire genome structure exhibited conservative features, such as the majority of start codons being the standard ATG codon and the majority of tRNA genes having the standard cloverleaf secondary structure. B. limnophila and B. quadrata showed collinearity in terms of sequence homology. Phylogenetic analysis indicates that the clade formed by the genera Margarya, Cipangopaludina, and Bellamya is the sister group of the genus Viviparus; Bellamya limnophila is more closely related to B. quadrata than to other species. This study contributes to the mitochondrial genome database of the family Viviparidae and provides valuable insights into the phylogenetic relationships of related snails. Full article

Soil salinity is rapidly spreading across agricultural regions and has become one of the most critical constraints on soybean growth, yield, and sustainable production. Despite the central role of transcription factors (TFs) in coordinating plant responses to abiotic stresses, the molecular mechanisms by which RWP-RK domain-containing TFs regulate salt-tolerant responses in soybean remain poorly understood. Our previous genome-wide characterization identified 28 RWP-RK TFs in soybean exhibiting abiotic stress-responsive expression, yet their biological functions under salt stress have not been experimentally validated. Here, we investigated a 981-bp GmRWP-RK1 encoding region and demonstrated its regulatory role in enhancing salt tolerance by activating antioxidant defence, Na⁺/K⁺ homeostasis, and transcriptional control of salt-responsive genes using a cross-species overexpression approach. The two Arabidopsis lines (OE1 & OE4) overexpressing GmRWP-RK1 demonstrated significantly improved salt tolerance, as evidenced by ~18% greater survival and enhanced germination compared to non-transgenic plants under salinity stress. This phenotype was supported by stronger antioxidant protection, as indicated by elevated proline levels, reduced MDA accumulation, and increased SOD and POD activities. At the molecular level, the transgenic lines also showed up-regulated expression of key stress-responsive genes (AtACS10, AtSUMO1, AtGBF1), confirming the regulatory influence of GmRWP-RK1 on salt-adaptation pathways. Consistent with the Arabidopsis results, GmRWP-RK1 overexpression in soybean hairy roots also led to improved salt-stress tolerance by accumulating significantly reduced ROS contents (27.38% lower H₂O₂ and 33.98% lower O₂⁻), and maintained a balanced Na⁺/K⁺ ratio compared to that of non-transgenic hairy roots under salinity. Furthermore, GmRWP-RK1-overexpressing transgenic soybean hairy roots showed increased expression of stress-responsive genes, especially GmATG-5, GmOLP-1, and GmOLP-2. Overall, our results support a possible role of GmRWP-RK1 in soybean salt tolerance and provide a foundation for future functional and breeding-oriented studies. Full article

CD8⁺ memory T (T_M) cells are essential for vaccine-induced protective immunity. While transforming growth factor beta (TGF-β) triggers CD8⁺ T_M cell differentiation, the underlying molecular mechanism(s) has yet to be uncovered. We therefore used a well-established cell culture protocol to prepare TGF-β-triggered CD8⁺ T_M cells derived from chicken ovalbumin (OVA)-specific T cell receptor (TCR) transgenic OTI mice, and systematically characterized them using Western blotting, confocal microscopy, flow cytometry and Seahorse assay analyses. We found that TGF-β/T cells exhibit a T_M cell phenotype (CD62L⁺KLRG1⁻) and display long-term survival upon adoptive transfer into mice. To elucidate the signaling circuitry underpinning the observed transcriptional and metabolic changes required to promote CD8⁺ T_M cell differentiation, we measured the expression of several critical factors and found that TGF-β triggered weak mTORC1 (mTORC1^Weak) signaling. mTORC1^Weak signaling in turn led to an increase in the abundance of key transcriptional (TCF1, FOXO1 and Eomes) and metabolic (AMPK-α1, ATG7, ULK1, SIRT1, OPA1 and LAL) factors and an elevation in mitochondrial mass and reliance on fatty acid oxidation (FAO). Our data thus reveal for the first time that TGF-β regulates CD8⁺ T cell memory by triggering mTORC1^Weak-mediated activation of the transcriptional FOXO1-TCF1-Eomes and metabolic AMPK-ULK1-ATG7 pathways. Given that induction of more qualified CD8⁺ T_M cells is one of the ultimate goals of vaccination, our findings identify additional targets critical to TGF-β-induced T cell memory, which may greatly impact future vaccine development for the treatment of cancer and infectious diseases. Full article