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Small Open Reading Frames (smORFs) of less than 100 codons remain mostly uncharacterised. About a thousand smORFs per genome encode peptides and microproteins about 70–80 aa long, often containing recognisable protein structures and markers of translation, and these are referred to as short Coding Sequences (sCDSs). The characterisation of individual sCDSs has provided examples of smORFs' function and conservation, but we cannot infer the functionality of all other metazoan smORFs from these. sCDS function has been characterised at a genome-wide scale in yeast and bacteria, showing that hundreds can produce a phenotype, but attempts in metazoans have been less successful. Either most sCDSs are not functional, or classic experimental techniques do not work with smORFs due to their shortness. Here, we combine extensive proteomics with bioinformatics and genetics in order to detect and corroborate sCDS function in Drosophila. Our studies nearly double the number of sCDSs with detected peptides and microproteins and an experimentally corroborated function. Finally, we observe a correlation between proven sCDS protein function and bioinformatic markers such as conservation and GC content. Our results support that sCDSs peptides and microproteins act as membrane-related regulators of canonical proteins, regulators whose functions are best understood at the cellular level, and whose mutants produce little, if any, overt morphological phenotypes. [ABSTRACT FROM AUTHOR]

Mitochondria shape intracellular Ca2+ signaling through the concerted activity of Ca2+ uptake via mitochondrial calcium uniporters and efflux by Na+/Ca2+ exchangers (NCLX). Here, we describe a novel relationship among NCLX, intracellular Ca2+, and autophagic activity. Conditions that stimulate autophagy in vivo and in vitro, such as caloric restriction and nutrient deprivation, upregulate NCLX expression in hepatic tissue and cells. Conversely, knockdown of NCLX impairs basal and starvation‐induced autophagy. Similarly, acute inhibition of NCLX activity by CGP 37157 affects bulk and endoplasmic reticulum autophagy (ER‐phagy) without significant impacts on mitophagy. Mechanistically, CGP 37157 inhibited the formation of FIP200 puncta and downstream autophagosome biogenesis. Inhibition of NCLX caused decreased cytosolic Ca2+ levels, and intracellular Ca2+ chelation similarly suppressed autophagy. Furthermore, chelation did not exhibit an additive effect on NCLX inhibition of autophagy, demonstrating that mitochondrial Ca2+ efflux regulates autophagy through the modulation of Ca2+ signaling. Collectively, our results show that the mitochondrial Ca2+ extrusion pathway through NCLX is an important regulatory node linking nutrient restriction and autophagy regulation. [ABSTRACT FROM AUTHOR]

Macroautophagy/autophagy is a highly conserved catabolic process vital for cellular stress responses and maintaining equilibrium within the cell. Malfunctioning autophagy has been implicated in the pathogenesis of various diseases, including certain neurodegenerative disorders, diabetes, metabolic diseases, and cancer. Cells face diverse metabolic challenges, such as limitations in nitrogen, carbon, and minerals such as phosphate and iron, necessitating the integration of complex metabolic information. Cells utilize a signal transduction network of sensors, transducers, and effectors to coordinate the execution of the autophagic response, concomitant with the severity of the nutrient‐starvation condition. This review presents the current mechanistic understanding of how cells regulate the initiation of autophagy through various nutrient‐dependent signaling pathways. Emphasizing findings from studies in yeast, we explore the emerging principles that underlie the nutrient‐dependent regulation of autophagy, significantly shaping stress‐induced autophagy responses under various metabolic stress conditions. [ABSTRACT FROM AUTHOR]

Dental stem cells (DSCs) have attracted significant interest as autologous stem cells since they are easily accessible and give a minimal immune response. These properties and their ability to both maintain self-renewal and undergo multi-lineage differentiation establish them as key players in regenerative medicine. While many regulatory factors determine the differentiation trajectory of DSCs, prior research has predominantly been based on genetic, epigenetic, and molecular aspects. Recent evidence suggests that DSC differentiation can also be influenced by autophagy, a highly conserved cellular process responsible for maintaining cellular and tissue homeostasis under various stress conditions. This comprehensive review endeavors to elucidate the intricate regulatory mechanism and relationship between autophagy and DSC differentiation. To achieve this goal, we dissect the intricacies of autophagy and its mechanisms. Subsequently, we elucidate its pivotal roles in impacting DSC differentiation, including osteo/odontogenic, neurogenic, and angiogenic trajectories. Furthermore, we reveal the regulatory factors that govern autophagy in DSC lineage commitment, including scaffold materials, pharmaceutical cues, and the extrinsic milieu. The implications of this review are far-reaching, underpinning the potential to wield autophagy as a regulatory tool to expedite DSC-directed differentiation and thereby promote the application of DSCs within the realm of regenerative medicine. [ABSTRACT FROM AUTHOR]

Regulating autophagy to control the homeostatic recycling process of cancer cells is a promising anticancer strategy. Golgi apparatus is a substrate of autophagy but the Golgi‐autophagy (Golgiphagy) mediated antitumor pathway is rarely reported. Herein, we have developed a novel Golgi‐targeted platinum (II) complex Pt3, which is ca. 20 times more cytotoxic to lung carcinoma than cisplatin and can completely eliminate tumors after intratumoral administration in vivo. Its nano‐encapsulated system for tail vein administration also features a good anti‐tumor effect. Mechanism studies indicate that Pt3 induces substantial Golgi stress, indicated by the fragmentation of Golgi structure, down‐regulation of Golgi proteins (GM130, GRASP65/55), loss of Golgi‐dependent transport and glycosylation. This triggers Golgiphagy but blocks the subsequent fusion of autophagosomes with lysosomes, that is a dual role in autophagy regulation, resulting in loss of proteostasis and apoptotic cell death. As far as we know, Pt3 is the first Golgi‐targeted Pt complex that can trigger Golgi stress‐mediated dual‐regulation of autophagic flux and autophagy‐apoptosis crosstalk for highly efficient cancer therapy. [ABSTRACT FROM AUTHOR]

Regulating autophagy to control the homeostatic recycling process of cancer cells is a promising anticancer strategy. Golgi apparatus is a substrate of autophagy but the Golgi‐autophagy (Golgiphagy) mediated antitumor pathway is rarely reported. Herein, we have developed a novel Golgi‐targeted platinum (II) complex Pt3, which is ca. 20 times more cytotoxic to lung carcinoma than cisplatin and can completely eliminate tumors after intratumoral administration in vivo. Its nano‐encapsulated system for tail vein administration also features a good anti‐tumor effect. Mechanism studies indicate that Pt3 induces substantial Golgi stress, indicated by the fragmentation of Golgi structure, down‐regulation of Golgi proteins (GM130, GRASP65/55), loss of Golgi‐dependent transport and glycosylation. This triggers Golgiphagy but blocks the subsequent fusion of autophagosomes with lysosomes, that is a dual role in autophagy regulation, resulting in loss of proteostasis and apoptotic cell death. As far as we know, Pt3 is the first Golgi‐targeted Pt complex that can trigger Golgi stress‐mediated dual‐regulation of autophagic flux and autophagy‐apoptosis crosstalk for highly efficient cancer therapy. [ABSTRACT FROM AUTHOR]

Autophagy is a multi-step lysosomal degradation process, which regulates energy and material metabolism and has been used to maintain homeostasis. Autophagy has been shown to be involved in the regulation of health and disease. But at present, there is no consensus on the relationship between autophagy and tumour, and we consider that it plays a dual role in the occurrence and development of tumour. That is to say, under certain conditions, it can inhibit the occurrence of tumour, but it can also promote the process of tumour. Therefore, autophagy could be used as a target for tumour treatment. The regulation of autophagy plays a synergistic role in the radiotherapy, chemotherapy, phototherapy and immunotherapy of tumour, and nano drug delivery system provides a promising strategy for improving the efficacy of autophagy regulation. This review summarised the progress in the regulatory pathways and factors of autophagy as well as nanoformulations as carriers for the delivery of autophagy modulators. [ABSTRACT FROM AUTHOR]

This study investigates the role of autophagy regulation in modulating neuroinflammation and cognitive function in an Alzheimer's disease (AD) mouse model with chronic cerebral hypoperfusion (CCH). Using the APP23/PS1 mice plus CCH model, we examined the impact of autophagy regulation on cognitive function, neuroinflammation, and autophagic activity. Our results demonstrate significant cognitive impairments in AD mice, exacerbated by CCH, but mitigated by treatment with the autophagy inhibitor 3-methyladenine (3-MA). Dysregulation of autophagy-related proteins, accentuated by CCH, underscores the intricate relationship between cerebral blood flow and autophagy dysfunction in AD pathology. While 3-MA restored autophagic balance, rapamycin (RAPA) treatment did not induce significant changes, suggesting alternative therapeutic approaches are necessary. Dysregulated microglial polarization and neuroinflammation in AD+CCH were linked to cognitive decline, with 3-MA attenuating neuroinflammation. Furthermore, alterations in M2 microglial polarization and the levels of inflammatory markers NLRP3 and MCP1 were observed, with 3-MA treatment exhibiting potential anti-inflammatory effects. Our findings shed light on the crosstalk between autophagy and neuroinflammation in AD+CCH and suggest targeting autophagy as a promising strategy for mitigating neuroinflammation and cognitive decline in AD+CCH. [ABSTRACT FROM AUTHOR]

Macroautophagy is a lysosomal degradative pathway or recycling process that maintains cellular homeostasis. This autophagy involves a series of sequential processing events, such as initiation; elongation and nucleation of the isolation membrane; cargo recruitment and maturation of the autophagosome (AP); transport of the AP; docking and fusion of the AP with a late endosome or lysosome; and regeneration of the lysosome by the autophagic lysosomal reformation cycle. These events are critically coordinated by the action of a set of several key components, including autophagy‐related proteins (Atg), and regulated by intricate networks, such as mechanistic target of rapamycin (mTOR), a master regulator of autophagy, as well as mTOR‐independent signaling pathways. Among mTOR‐independent pathways, the transient receptor potential (TRP) calcium ion channel TRPML (mucolipin) subfamily is emerging as an important signaling channel to modulate lysosomal biogenesis and autophagy. This review discusses the recent advances in elucidating the molecular mechanisms and regulation of the autophagy process. Understanding these mechanisms may ultimately allow scientists and clinicians to control this process in order to improve human health. [ABSTRACT FROM AUTHOR]

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) that links extracellular signals to the control of cell survival, growth, proliferation and differentiation. Due to its frequent overexpression and hyperactivation, EGFR has been a therapeutic target for human malignancies. Unfortunately, the specialized inhibitors of EGFR or EGFR-mediated pathways have not yet achieved the desired clinical effects. Therefore, it is necessary to elucidate the EGFR-mediated molecular basis of tumourigenesis, development and therapeutic resistance and to identify potential therapeutic targets. Interestingly, emerging research has indicated that autophagy is closely related to tumourigenesis, tumour progression and chemoresistance. Both autophagy upregulation and downregulation have been observed in cancers, suggesting its dual oncogenic and tumour suppressor properties during malignant transformation. Importantly, EGFR has been demonstrated to be a critical determinant of whether autophagy has a cytoprotective or cytotoxic effect. Therefore, here, we mainly focus on the function of EGFR in autophagy, especially the potential mechanism. The EGFR-mediated pathways or proteins involved in autophagy regulation include (1) the EGFR-mTOR pathway; (2) the EGFR-RAS pathway; (3) EGFR-Beclin1; (4) the EGFR-STAT3 pathway and (5) EGFR-LAPTM4B (oncoprotein lysosomal-associated transmembrane protein 4B). In addition, we also describe the role of EGFR-mediated autophagy in chemoresistance and tumour therapy. We attempt to summarized the mechanism by which EGFR-mediated signalling pathways participate in regulating autophagy and to investigate how to use the existing knowledge to identify potential cancer therapeutic targets. [ABSTRACT FROM AUTHOR]

Sonodynamic therapy (SDT) is a new non-invasive treatment method proposed based on photodynamic therapy (PDT). It has advantages such as high precision, strong tissue penetration, minimal side effects, and good patient compliance. With the maturation of nanomedicine, the application of nanosonosensitizers has further propelled the development of SDT. In recent years, people have developed many new types of sonosensitizers and explored the mechanisms of SDT. Among them, the studies about the relationship between autophagy and SDT have attracted increasing attention. After the SDT, cells usually undergo autophagy as a self-protective mechanism to resist external stimuli and reduce cell damage, which is beneficial for the treatment of atherosclerosis (AS), diabetes, and myocardial infarction but counterproductive in cancer treatment. However, under certain treatment conditions, excessive upregulation of autophagy can also promote cell death, which is beneficial for cancer treatment. This article reviews the latest research progress on the relationship between SDT and autophagy in cancers, AS, diabetes, and myocardial infarction. We also discuss and propose the challenges and prospects in enhancing SDT efficacy by regulating autophagy, with the hope of promoting the development of this promising therapeutic approach. [Display omitted] [ABSTRACT FROM AUTHOR]

Autophagy is a eukaryotic catabolic pathway essential for growth and development. In plants, it is activated in response to environmental cues or developmental stimuli. However, in contrast to other eukaryotic systems, we know relatively little regarding the molecular players involved in autophagy and the regulation of this complex pathway. In the framework of the COST (European Cooperation in Science and Technology) action TRANSAUTOPHAGY (2016-2020), we decided to review our current knowledge of autophagy responses in higher plants, with emphasis on knowledge gaps. We also assess here the potential of translating the acquired knowledge to improve crop plant growth and development in a context of growing social and environmental challenges for agriculture in the near future. [ABSTRACT FROM AUTHOR]

Doxorubicin (Dox) is an effective anti-cancer agent but limited by its cardiotoxicity, thus the search for pharmacological agents for enhancing anti-cancer activities and protecting against cardiotoxicity has been a subject of great interest. We have previously reported the synergistic anti-cancer effects of a novel compound DT-010. In the present study, we further investigated the cardioprotective effects of DT-010 in zebrafish embryos in vivo and the molecular underlying mechanisms in H9c2 cardiomyocytes in vitro. We showed that DT-010 prevented the Dox-induced morphological distortions in the zebrafish heart and the associated cardiac impairments, and especially improved ventricular functions. By using H9c2 cells model, we showed that DT-010 directly inhibited the generation of reactive oxygen species by Dox and protected cell death and cellular damage. We further observed that DT-010 protected against Dox-induced myocardiopathy via inhibiting downstream molecular pathways in response to oxidative stress, including reactive oxygen species-mediated MAPK signaling pathways ERK and JNK, and apoptotic pathways involving the activation of caspase 3, caspase 7, and PARP signaling. Recent studies also suggest the importance of alterations in cardiac autophagy in Dox cardiotoxicity. We further showed that DT-010 could inhibit the induction of autophagosomes formation by Dox via regulating the upstream Akt/AMPK/mTOR signaling. Since Dox-induced cardiotoxicity is multifactorial, our results suggest that multi-functional agent such as DT-010 might be an effective therapeutic agent for combating cardiotoxicity associated with chemotherapeutic agents such as Dox. [ABSTRACT FROM AUTHOR]

[Display omitted] • A multi-effect synergistic nanosystem was prepared upon biomimetic mineralization. • The nanosystem realized synergistic glycolysis-oxidative stress-autophagy regulation. • The nanosystem showed remarkable inhibitory effect on melanoma and lung metastasis. The complex, invasive, and metastatic nature of malignant tumors make the current treatment of patients challenging in advanced stages. The present study proposes a multi-effect synergistic biomimetic mineralization nanosystem (LND-BSA@FePO 4) to regulate tumor cell metabolism and relevant biological behaviors through glycolysis-oxidative stress-autophagy process. Bovine serum albumin complexed with lonidamine served as a template to induce the formation of iron phosphate mineralization in situ. After intratumoral administration, the released lonidamine inhibited hexokinase II and down-regulated the level of glycolysis, cutting off the energy and biosynthesis supply source for tumor growth. Ferric ions dissociated from biomineralization in acidic microenvironment converted reduced glutathione to oxidized glutathione, elevated oxidative stress and induced ferroptosis through chemokinetic reactions. The dissociated phosphate ions function as an autophagy inhibitor to block the protective autophagy cased by energy deprivation for efficacy enhancement. The up-regulation of Nrf2 and LC3 proteins, the down-regulation of HK2 and GPX4 proteins, and the increase of ROS level in tumors all confirmed this conclusion. Notably, the nanosystem also down-regulated the release of inflammatory factors (IL-6, IL-8) and metastasis-related proteins (N-Cadherine, Vimentin) simultaneously, effectively preventing distant lung metastasis of tumor. In summary, this biomineralization-based nanosystem exhibited powerful antitumor effects both in vitro and in vivo and provides a new perspective for addressing the dilemma of malignant tumor treatment. [ABSTRACT FROM AUTHOR]

Glioblastomas are the deadliest type of brain cancer and are frequently associated with poor prognosis and a high degree of recurrence despite removal by surgical resection and treatment by chemo- and radio-therapy. Photodynamic therapy (PDT) is a treatment well known to induce mainly necrotic and apoptotic cell death in solid tumors. 5-Aminolevulinic acid (5-ALA)-based PDT was recently shown to sensitize human glioblastoma cells (LN-18) to a RIP3 (Receptor Interacting Protein 3)-dependent cell death which is counter-acted by activation of autophagy. These promising results led us to investigate the pathways involved in cell death and survival mechanisms occurring in glioblastoma following PDT. In the present study, we describe a new TSC2 (Tuberous Sclerosis 2)-dependent survival pathway implicating MK2 (MAPKAPK2) kinase and 14-3-3 proteins which conducts to the activation of a pro-survival autophagy. Moreover, we characterized a new RIP3/TSC2 complex where RIP3 is suggested to promote cell death by targeting TSC2-dependent survival pathway. These results highlight (i) a new role of TSC2 to protect glioblastoma against PDT-induced cell death and (ii) TSC2 and 14-3-3 as new RIP3 partners. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging evidence indicates that the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome is activated, which results in a cytokine storm at the late stage of COVID-19. Autophagy regulation is involved in the infection and replication of SARS-CoV-2 at the early stage and the inhibition of NLRP3 inflammasome-mediated lung inflammation at the late stage of COVID-19. Here, we discuss the autophagy regulation at different stages of COVID-19. Specifically, we highlight the therapeutic potential of autophagy activators in COVID-19 by inhibiting the NLRP3 inflammasome, thereby avoiding the cytokine storm. We hope this review provides enlightenment for the use of autophagy activators targeting the inhibition of the NLRP3 inflammasome, specifically the combinational therapy of autophagy modulators with the inhibitors of the NLRP3 inflammasome, antiviral drugs, or anti-inflammatory drugs in the fight against COVID-19. [Display omitted] • Targeting the NLRP3 inflammasome and its inhibitors for the treatment of COVID-19. • Autophagy regulation and the use of its modulators at different stages of COVID-19 • Targeting the inhibition of NLRP3 inflammasome using autophagy inducers in COVID-19 [ABSTRACT FROM AUTHOR]

Hepatic fibrosis is a key pathological process of chronic liver diseases, caused by alcohol, toxic and aberrant energy metabolism. It progresses to cirrhosis or even hepatic carcinoma without effective treatment. Studies have shown that autophagy has important regulatory effects on hepatic stellate cells (HSCs) energy metabolism, and then affect the activation state of HSCs. Autophagy maintains hepatic energy homeostasis, and the dysregulation of autophagy can lead to the activation of HSCs and the occurrence and development of hepatic fibrosis. It is necessary to explore the mechanism of autophagy in energy metabolism-related hepatic fibrosis. Herein, the current study summarizes the regulating mechanisms of autophagy through different targets and signal pathways in energy metabolism-related hepatic fibrosis, and discusses the regulatory effect of autophagy by natural plant-derived, endogenous and synthetic compounds for the treatment of hepatic fibrosis. A better comprehension of autophagy in hepatic stellate cells energy metabolism-related hepatic fibrosis may provide effective intervention of hepatic fibrosis, explore the potential clinical strategies and promote the drug treatment of hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Abstract: Autophagy is an evolutionarily conserved process whereby cytoplasm and cellular organelles are degraded in lysosomes for amino acid and energy recycling. Autophagy is a survival pathway activated in response to nutrient deprivation and other stressful stimuli, such as metabolic stress and exposure to anticancer drugs. However, autophagy may also result in cell death, if it proceeds to completion. Defective autophagy is implicated in tumorigenesis, as the essential autophagy regulator beclin 1 is monoallelically deleted in human breast, ovarian and prostate cancers, and beclin 1+/− mice are tumor-prone. How autophagy suppresses tumorigenesis is under intense investigation. Cell-autonomous mechanisms, involving protection of genome integrity and stability, and a non-cell-autonomous mechanism, involving suppression of necrosis and inflammation, have been discovered so far. The role of autophagy in treatment responsiveness is also complex. Autophagy inhibition concurrently with chemotherapy or radiotherapy has emerged as a novel approach in cancer treatment, as autophagy-competent tumor cells depend on autophagy for survival under drug- and radiation-induced stress. Alternatively, autophagy stimulation and preservation of cellular fitness by maintenance of protein and organelle quality control, suppression of DNA damage and genomic instability, and limitation of necrosis-associated inflammation may play a critical role in cancer prevention. [Copyright &y& Elsevier]

Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related death worldwide. The three entirely variable entities have distinct epidemiology, molecular characteristics, prognosis, and strategies for clinical management. However, many gastric tumors appear to be resistant to current chemotherapeutic agents. Moreover, a significant number of gastric cancer patients, with a lack of optimal treatment strategies, have reduced survival. In recent years, multiple research data have highlighted the importance of autophagy, an essential catabolic process of cytoplasmic component digestion, in cancer. The role of autophagy as a tumor suppressor or tumor promoter mechanism remains controversial. The multistep nature of the autophagy process offers a wide array of targetable points for designing novel chemotherapeutic strategies. The purpose of this review is to summarize the current knowledge regarding the interplay between gastric cancer development and the autophagy process and decipher the role of autophagy in this kind of cancer. A plethora of different agents that direct or indirect target autophagy may be a novel therapeutic approach for gastric cancer patients. [ABSTRACT FROM AUTHOR]

Autophagy is a process of self-degradation that enables the cell to survive when faced with starvation or stressful conditions. The mechanistic target of rapamycin (mTOR), also known as the mammalian target of rapamycin, plays a critical role in maintaining a balance between cellular anabolism and catabolism. mTOR complex 1 (mTORC1) was unveiled as a master regulator of autophagy since inhibition of mTORC1 was required to initiate the autophagy process. Evidence has emerged in recent years to indicate that mTORC1 also directly regulates the subsequent steps of the autophagy process, including the nucleation, autophagosome elongation, autophagosome maturation and termination. By phosphorylating select protein targets of the autophagy core machinery and/or their regulators, mTORC1 can alter their functions, increase their proteasomal degradation or modulate their acetylation status, which is a key switch of the autophagy process. Moreover, it phosphorylates and alters the subcellular localization of transcription factors to suppress the expression of genes needed for autophagosome formation and lysosome biogenesis. The purpose of this review article is to critically analyze current literatures to provide an integrated view of how mTORC1 regulates various steps of the autophagy process. [ABSTRACT FROM AUTHOR]

Overnutrition in modern society has created many pathological conditions that have personal and social consequences. Fatty liver is one of such conditions that used to be considered transient and benign but is now known to be the beginning stage of more severe liver diseases. Excess lipids due to overnutrition are usually manifested in the liver by the appearance of subcellular structures known as lipid droplets (LD). LD are composed of a monolayer of phospholipids wrapping around a neutral lipid core mostly comprised of triglyceride (TG). TG is classically known to be catabolized by lipolytic-enzymes, such as Triglyceride lipase (ATGL), Hormone-sensitive lipase (HSL). This study describes a new mechanism of TG catabolism not by lipases but through cellular scavenger system - autophagy. Through experimentation, data suggests LD is not only composed of lipids but also proteins that potentially regulate LD formation and catabolism. Plin2, one of the lipid droplet proteins, suggests a pivotal role in the regulation of lipid levels in the liver via autophagy. Previous studies showed that in the absence of Plin2 the hepatic TG level reduced to only 50% of the control. Results from western blotting and imaging analysis has identified Plin2-deficiency in correlation to increased autophagy activity. The absence of Plin2 on the LD concomitantly caused the elevation of other proteins such as ABHD5, and Plin5 on lipid droplets. By analyzing the TG levels and autophagy flux in different knockout combinations of these LD proteins there can be a more versed understanding of how autophagy regulates TG catabolism in the liver. [ABSTRACT FROM AUTHOR]