ArticleThe Journal of clinical investigation2014
Apolipoprotein O is mitochondrial and promotes lipotoxicity in heart.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 58 citations in OpenAlex.
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- Identification of Gestation-Specific Patterns of Physiological, Protein and Cell-Free RNA Injury Markers in a Sheep Model of Regulable Preterm Fetal Hypoxia.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- AAV9-mediated gene supplementation therapy prevents and rescues arrhythmogenic cardiomyopathy in Pnpla2-mutated mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- NLRP6 overexpression improves nonalcoholic fatty liver disease by promoting lipid oxidation and decomposition in hepatocytes through the AMPK/CPT1A/PGC1A pathway.Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Mitochondrial apolipoprotein MIC26 is a metabolic rheostat regulating central cellular fuel pathways.Life science alliance · 2024Article
- Elevated expression of APOO as a potential prognostic marker in breast cancer: insights from bioinformatic analysis and experimental validation.BMC medical genomics · 2024Article
- Apolipoprotein O modulates cholesterol metabolism via NRF2/CYB5R3 independent of LDL receptor.Cell death & disease · 2024Article
- MDSCs-derived GPR84 induces CD8Journal for immunotherapy of cancer · 2023Article
- MIC26 and MIC27 are bona fide subunits of the MICOS complex in mitochondria and do not exist as glycosylated apolipoproteins.PloS one · 2023Article
- Review
- Genetic Origins of the Two Canis lupus familiaris (Dog) Freight Dog Populations.The Journal of heredity · 2022Article
- Relationship Between Myocardial Injury and Expression of PGC-1α and Its Coactivators in Chronic Keshan Disease.Current medical science · 2022Article
- Role of apolipoprotein O in autophagy via the p38 mitogen-activated protein kinase signaling pathway in myocardial infarction.Clinics (Sao Paulo, Brazil) · 2022Article
- Intracellular Lipid Accumulation and Mitochondrial Dysfunction Accompanies Endoplasmic Reticulum Stress Caused by Loss of the Co-chaperoneFrontiers in cell and developmental biology · 2021Article
- MIC26 and MIC27 cooperate to regulate cardiolipin levels and the landscape of OXPHOS complexes.Life science alliance · 2020Article
- Arctic-adapted dogs emerged at the Pleistocene-Holocene transition.Science (New York, N.Y.) · 2020Article
- Microglial Homeostasis Requires Balanced CSF-1/CSF-2 Receptor Signaling.Cell reports · 2020Article
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- Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetic cardiomyopathy is a secondary complication of diabetes with an unclear etiology. Based on a functional genomic evaluation of obesity-associated cardiac gene expression, we previously identified and cloned the gene encoding apolipoprotein O (APOO), which is overexpressed in hearts from diabetic patients. Here, we generated APOO-Tg mice, transgenic mouse lines that expresses physiological levels of human APOO in heart tissue. APOO-Tg mice fed a high-fat diet exhibited depressed ventricular function with reduced fractional shortening and ejection fraction, and myocardial sections from APOO-Tg mice revealed mitochondrial degenerative changes. In vivo fluorescent labeling and subcellular fractionation revealed that APOO localizes with mitochondria. Furthermore, APOO enhanced mitochondrial uncoupling and respiration, both of which were reduced by deletion of the N-terminus and by targeted knockdown of APOO. Consequently, fatty acid metabolism and ROS production were enhanced, leading to increased AMPK phosphorylation and Ppara and Pgc1a expression. Finally, we demonstrated that the APOO-induced cascade of events generates a mitochondrial metabolic sink whereby accumulation of lipotoxic byproducts leads to lipoapoptosis, loss of cardiac cells, and cardiomyopathy, mimicking the diabetic heart-associated metabolic phenotypes. Our data suggest that APOO represents a link between impaired mitochondrial function and cardiomyopathy onset, and targeting APOO-dependent metabolic remodeling has potential as a strategy to adjust heart metabolism and protect the myocardium from impaired contractility.
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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 OpenQuestion graph.