Macroautophagy/autophagy, is widely recognized for its crucial role in enabling cell survival and maintaining cellular energy homeostasis during starvation or energy stress. Its regulation is intricately linked to cellular energy status. In this review, covering yeast, mammals, and plants, we aim to provide a comprehensive overview of the understanding of the roles and mechanisms of carbon- or glucose-deprivation related autophagy, showing how cells effectively respond to such challenges for survival. Further investigation is needed to determine the specific degraded substrates by autophagy during glucose or energy deprivation and the diverse roles and mechanisms during varying durations of energy starvation.Abbreviations: ADP: adenosine diphosphate; AMP: adenosine monophosphate; AMPK: AMP-activated protein kinase; ATG: autophagy related; ATP: adenosine triphosphate; ER: endoplasmic reticulum; ESCRT: endosomal sorting complex required for transport; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GD: glucose deprivation; GFP: green fluorescent protein; GTPases: guanosine triphosphatases; HK2: hexokinase 2; K phaffii: Komagataella phaffii; LD: lipid droplet; MAP1LC3/LC3: microtubule-associated protein1 light chain 3; MAPK: mitogen-activated protein kinase; Mec1: mitosis entry checkpoint 1; MTOR: mechanistic target of rapamycin kinase; NAD (+): nicotinamide adenine dinucleotide; OGD: oxygen and glucose deprivation; PAS: phagophore assembly site; PCD: programmed cell death; PtdIns3K: class III phosphatidylinositol 3-kinase; PtdIns3P: phosphatidylinositol-3-phosphate; ROS: reactive oxygen species; S. cerevisiae: Saccharomyces cerevisiae; SIRT1: sirtuin 1; Snf1: sucrose non-fermenting 1; STK11/LKB1: serine/threonine kinase 11; TFEB: transcription factor EB; TORC1: target of rapamycin complex 1; ULK1: unc-51 like kinase 1; Vps27: vacuolar protein sorting 27; Vps4: vacuolar protein sorting 4.

Forkhead box-O1 (FOXO1) is a downstream target of AKT and plays crucial roles in cell cycle control, apoptosis, metabolism and adipocyte differentiation. It is thought that FOXO1 affects adipocyte differentiation by regulating lipogenesis and cell cycle. With the deepening in the understanding of this field, it is currently believed that FOXO1 translocation between nuclei and cytoplasm is involved in the regulation of FOXO1 activity, thus affecting adipocyte differentiation. Translocation of FOXO1 depends on its post-translational modifications and interactions with 14-3-3. Based on these modifications and interactions, FOXO1 could regulate lipogenesis through PPARγ and the adipocyte cell cycle through p21 and p27. In this review, we aim to provide a comprehensive FOXO1 regulation network in adipocyte differentiation by linking together distinct functions mentioned above to explain their effects on adipocyte differentiation and to emphasize the regulatory role of FOXO1. In addition, we also focus on the novel findings such as the use of miRNAs in FOXO1 regulation and highlight the improvable issues, such as RNA modifications, for future research in the field.

Translocator protein (TSPO) is highly expressed in the cardiovascular system, exerting crucial effects on both myocardial damage and protection. However, the role and mechanism of TSPO in myocardial ischemia/reperfusion (I/R) injury remains elusive. In the current study, we subjected H9c2 cardiomyocytes to anoxia/reoxygenation (A/R) and knocked down TSPO expression by RNA interference to investigate the possible mechanism of TSPO on I/R injury. TSPO expression in cardiomyocytes was up-regulated when exposed to A/R, but normal in anoxic preconditioned (APC) cardiomyocytes. Moreover, A/R also led to an increase in reactive oxygen species (ROS), oxidative stress aggravation, mitochondrial membrane potential collapse, mitochondrial permeability transition pore (mPTP) opening, and cell apoptosis. However, these events were completely compensated by downregulating TSPO expression. TSPO-downregulated cardiomyocytes produced lesser lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), and showed lesser cytosol malondialdehyde (MDA) accumulation than normal cells after A/R injury. On the other hand, the TSPO- downregulated cells showed higher activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), mitochondrial function stabilization, resulting in less cell apoptosis and damage in case of A/R condition. In conclusion, TSPO expression is up-regulated under A/R injury, whereas repression of TSPO improves the endurance of cardiomyocytes against A/R injury by reducing oxidative stress, mitochondrial damage and cell apoptosis.

BACKGROUND: IgE has been known for mediating endothelial cell dysfunction and mast cell (MC) activation to fuel asthma-aggravated high-fat diet–induced atherosclerosis. However, it remains unclear for the mechanism of asthma-mediated atherosclerosis, especially the potential involvement of IgE in the exacerbation of asthma-mediated atherosclerosis with a standard laboratory diet, and the cross talk between endothelial cells and MCs. METHODS: Asthma-mediated atherosclerosis mice models under a standard laboratory diet and FcεR1 knock-out mice were used to determine the role of IgE-FcεR1 signaling in asthma-mediated atherosclerosis, which was assessed by Oil Red O staining and immunohistochemistry. Various in vitro assays including nanoparticle tracking analysis and transmission electron microscopy were used to evaluate exosome characteristics. Immunofluorescence and fluorescent in situ hybridization approaches were used to evaluate the effect and mechanism of MC-secreted exosomes encapsulated circular RNA CDR1as (cerebellar degeneration-related 1 antisense) on endothelial cells in vivo and in vitro. Finally, cohort studies examined the plasma CDR1as levels in patients with atherosclerosis with or without allergies. RESULTS: Asthma mice with a standard laboratory diet showed increased atherosclerotic lesions and inflammatory infiltration depending on IgE-FcεR1 signal. FcεR1 knockout mice and blockage of IgE-FcεR1 signaling with IgE monoclonal antibody, omalizumab, all significantly alleviated asthma-mediated atherosclerosis and vascular inflammatory remodeling. Anti-inflammation with dexamethasone and stabilization of MC with cromolyn partially alleviated atherosclerotic lesions and mitigated the inflammatory infiltration in arteries. Mechanistically, IgE stimulation upregulates MC CDR1as expression in exosomes and upregulates the endothelial cell adhesive factors VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1) via the CDR1as-FUS (fused in sarcoma)-phos-p65 axis. Knockdown of CDR1as in vivo significantly decreased the endothelial adhesion function and mitigated asthma-mediated atherosclerosis. Furthermore, a cohort study indicated higher plasma CDR1as levels in patients with atherosclerosis with allergies than in patients with atherosclerosis and healthy controls. CONCLUSIONS: Exosomes from IgE-stimulated MCs aggravated atherosclerosis through circular RNA CDR1as-mediated endothelial dysfunction, providing a novel insight into asthma-mediated atherosclerosis and potential diagnostic and therapeutic targets.

Epigallocatechin-3-gallate suppresses differentiation of adipocytes via regulating the phosphorylation of FOXO1 mediated by PI3K-AKT signaling in 3T3-L1 cells Epigallocatechin-3-gallate suppresses differentiation of adipocytes via regulating the phosphorylation of FOXO1 mediated by PI3K-AKT signaling in 3T3-L1 cells