Evidence
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
Autophagy. 2024 Jun 23:1-3. doi: 10.1080/15548627.2024.2356487. Online ahead of print.
ABSTRACT
Mutations in the DDHD2 (DDHD domain containing 2) gene cause autosomal recessive spastic paraplegia type 54 (SPG54), a rare neurodegenerative disorder characterized by the early childhood onset of progressive spastic paraplegia. DDHD2 is reported as the principal brain triacylglycerol (TAG) lipase whose dysfunction causes massive lipid droplet (LD) accumulation in the brains of SPG54 patients. However, the precise functions of DDHD2 in regulating LD catabolism are not yet fully understood. In a recent study, we demonstrate that DDHD2 interacts with multiple members of the Atg8-family proteins (MAP1LC3/LC3s, GABARAPs), which play crucial roles in lipophagy. DDHD2 possesses two LC3-interacting region (LIR) motifs that contribute to its LD-eliminating activity. Moreover, DDHD2 enhances the colocalization between LC3B and LDs to promote lipophagy. LD·ATTEC, a compound that tethers LC3 to LDs to enhance their macroautophagic/autophagic clearance, effectively counteracts DDHD2 deficiency-induced LD accumulation. These findings provide insights into the dual functions of DDHD2 as a TAG lipase and cargo receptor for lipophagy in neuronal LD catabolism, and also suggest a potential therapeutic approach for treating SPG54 patients.
PMID:38909316 | DOI:10.1080/15548627.2024.2356487
![Google](https://www.google.com/images/branding/googlelogo/2x/googlelogo_light_color_92x30dp.png)
![Google Keep](https://www.gstatic.com/images/branding/product/1x/keep_48dp.png)
![Share on Linkedin](https://psychiatryai.com/wp-content/uploads/2023/10/linkedin-logo-png-2048-1.png)
Estimated reading time: 4 minute(s)
Latest: Psychiatryai.com #RAISR4D Evidence
![](/wp-content/uploads/2024/04/bd462cc11bcf0bd0d0d6f1d0f8b7cd04-modified-1.png)
Cool Evidence: Engaging Young People and Students in Real-World Evidence
![](/wp-content/uploads/2024/04/bd462cc11bcf0bd0d0d6f1d0f8b7cd04-modified-1.png)
Real-Time Evidence Search [Psychiatry]
![](/wp-content/uploads/2024/04/pubmed.png)
AI Research
![](/wp-content/uploads/2024/05/Il5nR_nf_400x400-modified-1.png)
DDHD2 promotes lipid droplet catabolism by acting as a TAG lipase and a cargo receptor for lipophagy
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
🌐 90 Days
AI Virtual Reality Related Evidence Matrix
ZDHHC7-mediated S-palmitoylation of ATG16L1 facilitates LC3 lipidation and autophagosome formation Inhibition of autophagy prevents cardiac dysfunction at early stages of cardiomyopathy in Bag3-deficient hearts Astrocytic HILPDA promotes lipid droplets generation to drive cognitive dysfunction in mice with sepsis-associated encephalopathy Biallelic variants in LARS1 induce steatosis in developing zebrafish liver via enhanced autophagy Biallelic variants in LARS1 induce steatosis in developing zebrafish liver via enhanced autophagy An initial HOPS-mediated fusion event is critical for autophagosome transport initiation from the axon terminal Drop-On-Demand Microdroplet Generation under Charge Injection by Corona Discharge De novo and inherited monoallelic variants in TUBA4A cause ataxia and spasticity The link between alterations in circadian rhythms and lipid metabolism in bipolar disorder: the lipid droplets hypothesis ROS-mediated lysosomal membrane permeabilization and autophagy inhibition regulate bleomycin-induced cellular senescence Expression and localization of HSD17B13 along mouse urinary tract Expression and localization of HSD17B13 along mouse urinary tract Tau fibrils evade autophagy by excessive p62 coating and TAX1BP1 exclusion A novel bellidifolin intervention mitigates nonalcoholic fatty liver disease-like changes induced by bisphenol F Mechanisms of autophagy-lysosome dysfunction in neurodegenerative diseases Hepatic myelopathy neurological complication of chronic liver disease: two case reports (+)Alpha-Lipoic Acid Regulates Lipid Metabolism Gene Expression and Lipidic Profile in a Cellular Model of Fatty Acid Overload Massive traumatic epidural hematoma in a child with suprasellar arachnoid cyst and hydrocephalus Two new cases with the UBQLN2 gene mutation in Han Chinese Hsp90aa1/JUN/Ccl2 regulatory axis mediates migration and differentiation of NSPCs, promoting the onset and progression of early post-ischemic stroke epilepsy Lysosomal Channels as New Molecular Targets in the Pharmacological Therapy of Neurodegenerative Diseases via Autophagy Regulation Role of metabolic dysfunction and inflammation along the liver-brain axis in animal models with obesity-induced neurodegeneration Biallelic null variants in PNPLA8 cause microcephaly by reducing the number of basal radial glia Paraoxonase-2 agonist vutiglabridin promotes autophagy activation and mitochondrial function to alleviate non-alcoholic steatohepatitis A PNPLA3-Deficient iPSC-Derived Hepatocyte Screen Identifies Pathways to Potentially Reduce Steatosis in Metabolic Dysfunction-Associated Fatty Liver Disease miR-218-5p promotes hepatic lipogenesis through targeting Elovl5 in non-alcoholic fatty liver disease Haloacetamides disinfection by-products, a potential risk factor for nonalcoholic fatty liver disease Mechanistic Evaluation of miRNAs and Their Targeted Genes in the Pathogenesis and Therapeutics of Parkinson's Disease Screening of the Lipid-Lowering Probiotic Lactiplantibacillus Plantarum SDJ09 and its Anti-Obesity Mechanism Exploring the Significance of Microglial Phenotypes and Morphological Diversity in Neuroinflammation and Neurodegenerative Diseases: From Mechanisms to Potential Therapeutic Targets Review article: Hepatic steatosis and its associations with acute and chronic liver diseases Autosomal Recessive Guanosine Triphosphate Cyclohydrolase I Deficiency: Redefining the Phenotypic Spectrum and Outcomes Wulingsan Alleviates MAFLD by Activating Autophagy via Regulating the AMPK/mTOR/ULK1 Signaling Pathway Fahr's disease with neuropsychiatric symptoms and intermittent course: a case report Identification and bioinformatics analysis of a novel variant in the HERC2 gene in a patient with intellectual developmental disorder Identification and bioinformatics analysis of a novel variant in the HERC2 gene in a patient with intellectual developmental disorder Early-onset Alzheimer dementia superimposed on schizophrenia: a rare case report An N-terminal and ankyrin repeat domain interactome of Shank3 identifies the protein complex with the splicing regulator Nono in mice Aging exacerbates oxidative stress and liver fibrosis in an animal model of Down Syndrome Early-Onset Autosomal Dominant Myopathy with Vacuolated Fibers and Tubular Aggregates but No Periodic Paralysis, in a Patient with the c.1583G>A (p.R528H) mutation in the CACNA1S Gene Early-Onset Autosomal Dominant Myopathy with Vacuolated Fibers and Tubular Aggregates but No Periodic Paralysis, in a Patient with the c.1583G>A (p.R528H) mutation in the CACNA1S Gene Mutations in CLCN6 as a Novel Genetic Cause of Neuronal Ceroid Lipofuscinosis iTRAQ-Based Serum Proteomic Analysis Reveals Multifactorial Cellular Function Impairment and Aggravated Systematic Inflammation in Drug-free Obsessive-Compulsive Disorders iTRAQ-Based Serum Proteomic Analysis Reveals Multifactorial Cellular Function Impairment and Aggravated Systematic Inflammation in Drug-free Obsessive-Compulsive Disorders Constitutive and conditional epitope-tagging of endogenous G protein coupled receptors in Drosophila Constitutive and conditional epitope-tagging of endogenous G protein coupled receptors in Drosophila Dysregulation of Lipid Metabolism Serves as A Link Between Alzheimer's and Cardiovascular Disease, As Witnessed in A Cross-Sectional Study GRM7 deficiency, from excitotoxicity and neuroinflammation to neurodegeneration: Systematic review of GRM7 deficient patients Proteomic characterization of the medial prefrontal cortex in chronic restraint stress mice Cannabidiol protects mouse hippocampal neurons from neurotoxicity induced by amyloid β-peptide25-35 Mice with deficiency in Pcdh15, a gene associated with bipolar disorders, exhibit significantly elevated diurnal amplitudes of locomotion and body temperature An Epigenetic Manifestation of Alzheimer's Disease: DNA Methylation TMEM106B C-terminal fragments aggregate and drive neurodegenerative proteinopathy Hepatic-specific Pgc-1α ablation drives fibrosis in a MASH model TGR5 deficiency in excitatory neurons ameliorates Alzheimer's pathology by regulating APP processing Exploring the effect and mechanism of Hippophae rhamnoides L. triterpenoid acids on improving NAFLD based on network pharmacology and experimental validation in vivo and in vitro Exploring the effect and mechanism of Hippophae rhamnoides L. triterpenoid acids on improving NAFLD based on network pharmacology and experimental validation in vivo and in vitro TIR8 Protects Against Nonalcoholic Steatohepatitis by Antagonizing Lipotoxicity-induced PPARα Downregulation and Reducing the Sensitivity of Hepatocytes to LPS TIR8 Protects Against Nonalcoholic Steatohepatitis by Antagonizing Lipotoxicity-induced PPARα Downregulation and Reducing the Sensitivity of Hepatocytes to LPS Faecal proteomics links neutrophil degranulation with mortality in patients with alcohol-associated hepatitis A unique case of hyperammonemia due to CA5A deficiency: Impact of coexisting gene mutations, pseudogene, and microdeletion Assessment of the disruption effects of tetrabromobisphenol A and its analogues on lipid metabolism using multiple in vitro models Assessment of the disruption effects of tetrabromobisphenol A and its analogues on lipid metabolism using multiple in vitro models CPT1A loss disrupts BCAA metabolism to confer therapeutic vulnerability in TP53-mutated liver cancer
Evidence Blueprint
DDHD2 promotes lipid droplet catabolism by acting as a TAG lipase and a cargo receptor for lipophagy
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
☊ AI-Driven Related Evidence Nodes
(recent articles with at least 5 words in title)
More Evidence
![](https://psychiatryai.com/wp-content/uploads/2023/04/psychiatryai_com.webp)
DDHD2 promotes lipid droplet catabolism by acting as a TAG lipase and a cargo receptor for lipophagy
🌐 365 Days
AI Virtual Reality Related Evidence Matrix
The DDHD2-STXBP1 interaction mediates long-term memory via generation of saturated free fatty acids Exercise ameliorates lipid droplet metabolism disorder by the PLIN2-LIPA axis-mediated lipophagy in mouse model of non-alcoholic fatty liver disease Triacylglycerol uptake and handling by macrophages: From fatty acids to lipoproteins Expanding SPG18 clinical spectrum: autosomal dominant mutation causes complicated hereditary spastic paraplegia in a large family Relationship between brain white matter damage and grey matter atrophy in hereditary spastic paraplegia types 4 and 5 Long-term clinical observation of patients with heterozygous KIF1A variants Regulation of Benzo[a]pyrene-Induced Hepatic Lipid Accumulation through CYP1B1-Induced mTOR-Mediated Lipophagy Phospholipase Modulation of Synaptic Membrane Landscape: Driving Force Behind Memory Formation? Accumulation of neutral lipids in dystrophic neurites surrounding amyloid plaques in Alzheimer's disease Correction of symptoms of Huntington disease by genistein through FOXO3-mediated autophagy stimulation A metabolically controlled contact site between vacuoles and lipid droplets in yeast Neuroinflammatory disease signatures in SPG11-related hereditary spastic paraplegia patients The fatty liver disease-causing protein PNPLA3-I148M alters lipid droplet-Golgi dynamics ZDHHC7-mediated S-palmitoylation of ATG16L1 facilitates LC3 lipidation and autophagosome formation Epigenetic regulation of autophagy-related genes: Implications for neurodevelopmental disorders 4R MAPT/tau drives endolysosomal and autophagy dysfunction in frontotemporal dementia BNIP3 in hypoxia-induced mitophagy: novel insights and promising target for non-alcoholic fatty liver disease Metabolic changes and propensity for inflammation, fibrosis, and cancer in livers of mice lacking lysosomal acid lipase Inhibition of autophagy prevents cardiac dysfunction at early stages of cardiomyopathy in Bag3-deficient hearts LncRNA AK142643 promotes hepatic lipid accumulation by upregulating CD36 via interacting with IGF2BP2 The beneficial role of autophagy in multiple sclerosis: yes or no? Selenoprotein I is indispensable for ether lipid homeostasis and proper myelination Astrocytic HILPDA promotes lipid droplets generation to drive cognitive dysfunction in mice with sepsis-associated encephalopathy Phosphorylation-state dependent intraneuronal sorting of Aβ differentially impairs autophagy and the endo-lysosomal system Altered lipid homeostasis is associated with cerebellar neurodegeneration in SNX14 deficiency Perilipin 2 inhibits replication of hepatitis B virus deoxyribonucleic acid by regulating autophagy under high-fat conditions The multifaceted functions of β-arrestins and their therapeutic potential in neurodegenerative diseases Case of Hallervorden-Spatz Syndrome: A Tale of Twin Sisters Hereditary spastic paraparesis type 46 (SPG46): new GBA2 variants in a large Italian case series and review of the literature A rare case of adult-onset spastic paraparesis associated with Klinefelter syndrome Biallelic variants in LARS1 induce steatosis in developing zebrafish liver via enhanced autophagy Biallelic variants in LARS1 induce steatosis in developing zebrafish liver via enhanced autophagy Neurologic involvement in cystinosis: Focus on brain lesions and new evidence of four-repeat (4R-) Tau immunoreactivity An initial HOPS-mediated fusion event is critical for autophagosome transport initiation from the axon terminal Drop-On-Demand Microdroplet Generation under Charge Injection by Corona Discharge Naringin Protects against Non-Alcoholic Fatty Liver Disease by Promoting Autophagic Flux and Lipophagy De novo and inherited monoallelic variants in TUBA4A cause ataxia and spasticity Structural basis of lipid-droplet localization of 17-beta-hydroxysteroid dehydrogenase 13 Effects of riboflavin deficiency and high dietary fat on hepatic lipid accumulation: a synergetic action in the development of non-alcoholic fatty liver disease The link between alterations in circadian rhythms and lipid metabolism in bipolar disorder: the lipid droplets hypothesis Lipid Droplets Accumulation in the Brain of HIV Transgenic Rat: Implication in the Accelerated Aging of HIV Infected Individuals Dysfunction of autophagy in high-fat diet-induced nonalcoholic fatty liver disease Cyanotoxin cylindrospermopsin disrupts lipid homeostasis and metabolism in a 3D in vitro model of the human liver Brain Lipids and Lipid Droplet Dysregulation in Alzheimer's Disease and Neuropsychiatric Disorders ROS-mediated lysosomal membrane permeabilization and autophagy inhibition regulate bleomycin-induced cellular senescence Expression and localization of HSD17B13 along mouse urinary tract Expression and localization of HSD17B13 along mouse urinary tract The critical role of BTRC in hepatic steatosis as an ATGL E3 ligase Toxic gain-of-function mechanisms in C9orf72 ALS-FTD neurons drive autophagy and lysosome dysfunction Organophosphate ester flame retardants and plasticizers affect the phenotype and function of HepG2 liver cells Adipose triglyceride lipase gene expression in peripheral blood mononuclear cells of subjects with obesity and its association with insulin resistance, inflammation and lipid accumulation in liver Tau fibrils evade autophagy by excessive p62 coating and TAX1BP1 exclusion FBXL5 promotes lipid accumulation in alcoholic fatty liver disease by promoting the ubiquitination and degradation of TFEB Long-Term High-Fat Diet Consumption Aggravates β-Amyloid Deposition and Tau Pathology Accompanied by Microglial Activation in an Alzheimer's Disease Model Serotonin Signaling through Lipid Membranes A novel bellidifolin intervention mitigates nonalcoholic fatty liver disease-like changes induced by bisphenol F Mechanisms of autophagy-lysosome dysfunction in neurodegenerative diseases The role of lipid dysregulation in gestational diabetes mellitus: Early prediction and postpartum prognosis Role of Angiotensin II in Non-Alcoholic Steatosis Development Nuclear RNA catabolism controls endogenous retroviruses, gene expression asymmetry, and dedifferentiation Targeted degradation of SNCA/α-synuclein aggregates in neurodegeneration using the AUTOTAC chemical platform Integrative Metabolomics and Whole Transcriptome Sequencing Reveal Role for TREM2 in Metabolism Homeostasis in Alzheimer's Disease Hepatic myelopathy neurological complication of chronic liver disease: two case reports Selective autophagy associated with iron overload aggravates non-alcoholic steatohepatitis via ferroptosis