ArticleeLife2023
APOE expression and secretion are modulated by mitochondrial dysfunction.
Article in eLife, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Genetic and environmental risk factors for dementia in African adults: A systematic review.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Pooled it
- Aging of hematopoietic stem cells is inconsequential to progenitor cell function.Stem cell reports · 2026Article
- Mitochondrial Dynamics and SLC25 Transporters in Neurodegeneration: From Mechanisms to Therapeutic Opportunities.Biomolecules · 2026Review
- Distinct signaling mechanisms and proteome phenotypes are elicited by compartment-specific genetic defects of copper homeostasis.bioRxiv : the preprint server for biology · 2026Article
- Is Hypothalamic Dysfunction a Cause of Type II Diabetes Mellitus?Neuroendocrinology · 2026Review
- Targeting mitochondrial transporters and metabolic reprogramming for disease treatment.Journal of translational medicine · 2025Review
- Nor1 and Mitophagy: An Insight into Sertoli Cell Function Regulating Spermatogenesis Using a Transgenic Rat Model.International journal of molecular sciences · 2025Article
- Fueling the brain - the role of apolipoprotein E in brain energy metabolism and its implications for Alzheimer's disease.Translational psychiatry · 2025Review
- Human cytomegalovirus induces neuronal gene expression through IE1 for viral maturation.Nature communications · 2025Article
- Lars2 Deficiency-Induced Mitochondrial Dysfunction Drives the Emergence of a Pro-Inflammatory Stroke-Specific Microglial Subpopulation.Aging and disease · 2025Article
- The Glutamate/GABA-Glutamine Cycle: Insights, Updates, and Advances.Journal of neurochemistry · 2025Review
- Adaptive protein synthesis in genetic models of copper deficiency and childhood neurodegeneration.Molecular biology of the cell · 2025Article
- The Role of Oligodendrocyte Lineage Cells in the Pathogenesis of Alzheimer's Disease.Neurochemical research · 2025Review
- Multi-functional role of apolipoprotein E in neurodegenerative diseases.Frontiers in aging neuroscience · 2025Review
- ApoE deficiency protects from mRNA vaccine-induced mitochondrial dysfunction at the injection site under metabolic stress.Theranostics · 2025Article
- Inhibiting mtDNA transcript translation alters Alzheimer's disease-associated biology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Adaptive protein synthesis in genetic models of copper deficiency and childhood neurodegeneration.bioRxiv : the preprint server for biology · 2024Article
- The mitochondrial citrate carrier SLC25A1 regulates metabolic reprogramming and morphogenesis in the developing heart.Communications biology · 2024Article
- The enhancer RNA, AANCR, regulates APOE expression in astrocytes and microglia.Nucleic acids research · 2024Article
- Integrative Analyses of Mitophagy-Related Genes and Mechanisms Associated with Type 2 Diabetes in Muscle Tissue.Current issues in molecular biology · 2024Article
Corrections and comments
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Authors and funding
27 authors at 5 institutions in 1 country.
Funding
Abstract
Mitochondria influence cellular function through both cell-autonomous and non-cell autonomous mechanisms, such as production of paracrine and endocrine factors. Here, we demonstrate that mitochondrial regulation of the secretome is more extensive than previously appreciated, as both genetic and pharmacological disruption of the electron transport chain caused upregulation of the Alzheimer's disease risk factor apolipoprotein E (APOE) and other secretome components. Indirect disruption of the electron transport chain by gene editing of SLC25A mitochondrial membrane transporters as well as direct genetic and pharmacological disruption of either complexes I, III, or the copper-containing complex IV of the electron transport chain elicited upregulation of APOE transcript, protein, and secretion, up to 49-fold. These APOE phenotypes were robustly expressed in diverse cell types and iPSC-derived human astrocytes as part of an inflammatory gene expression program. Moreover, age- and genotype-dependent decline in brain levels of respiratory complex I preceded an increase in APOE in the 5xFAD mouse model. We propose that mitochondria act as novel upstream regulators of APOE-dependent cellular processes in health and disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.