ArticleThe Biochemical journal2004
Alternative translation initiation generates a novel isoform of insulin-degrading enzyme targeted to mitochondria.
Article in The Biochemical journal, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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
78 citing papers in PubMed, 159 citations in OpenAlex.
- Genetic and clinical investigation of insulin-degrading enzyme in Parkinson's disease within the Chinese Han population.Frontiers in neuroscience · 2026Article
- Decreased expression of insulin-degrading enzyme increases gluconeogenesis and glucose production in cultured hepatocytes administered with glucagon.Scientific reports · 2025Article
- Insulin-Degrading Enzyme Regulates mRNA Processing and May Interact with the CCR4-NOT Complex.Cells · 2025Article
- Evaluation of Eukaryotic mRNA Coding Potential.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Somatostatin: Linking Cognition and Alzheimer Disease to Therapeutic Targeting.Pharmacological reviews · 2024Review
- Loss of WDR23 proteostasis impacts mitochondrial homeostasis in the mouse brain.Cellular signalling · 2024Article
- The Insulin-Degrading Enzyme from Structure to Allosteric Modulation: New Perspectives for Drug Design.Biomolecules · 2023Review
- N-terminal proteoforms may engage in different protein complexes.Life science alliance · 2023Article
- Insulin-Degrading Enzyme Interacts with Mitochondrial Ribosomes and Respiratory Chain Proteins.Biomolecules · 2023Article
- Sirt3 deficiency induced down regulation of insulin degrading enzyme in comorbid Alzheimer's disease with metabolic syndrome.Scientific reports · 2022Article
- Possible Role of Insulin-Degrading Enzyme in the Physiopathology of Retinitis Pigmentosa.Cells · 2022Article
- Review
- Inhibition of Insulin Degrading Enzyme to Control Diabetes Mellitus and its Applications on some Other Chronic Disease: a Critical Review.Pharmaceutical research · 2022Review
- An alternative downstream translation start site in the non-TIR adaptor Scimp enables selective amplification of CpG DNA responses in mouse macrophages.Immunology and cell biology · 2022Article
- Article
- Protein import in mitochondria biogenesis: guided by targeting signals and sustained by dedicated chaperones.RSC advances · 2021Review
- Article
- Article
- Targeting Insulin-Degrading Enzyme in Insulin Clearance.International journal of molecular sciences · 2021Review
- Modulation of Insulin Sensitivity by Insulin-Degrading Enzyme.Biomedicines · 2021Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
IDE (insulin-degrading enzyme) is a widely expressed zinc-metallopeptidase that has been shown to regulate both cerebral amyloid beta-peptide and plasma insulin levels in vivo. Genetic linkage and allelic association have been reported between the IDE gene locus and both late-onset Alzheimer's disease and Type II diabetes mellitus, suggesting that altered IDE function may contribute to some cases of these highly prevalent disorders. Despite the potentially great importance of this peptidase to health and disease, many fundamental aspects of IDE biology remain unresolved. Here we identify a previously undescribed mitochondrial isoform of IDE generated by translation at an in-frame initiation codon 123 nucleotides upstream of the canonical translation start site, which results in the addition of a 41-amino-acid N-terminal mitochondrial targeting sequence. Fusion of this sequence to the N-terminus of green fluorescent protein directed this normally cytosolic protein to mitochondria, and full-length IDE constructs containing this sequence were also directed to mitochondria, as revealed by immuno-electron microscopy. Endogenous IDE protein was detected in purified mitochondria, where it was protected from digestion by trypsin and migrated at a size consistent with the predicted removal of the N-terminal targeting sequence upon transport into the mitochondrion. Functionally, we provide evidence that IDE can degrade cleaved mitochondrial targeting sequences. Our results identify new mechanisms regulating the subcellular localization of IDE and suggest previously unrecognized roles for IDE within mitochondria.
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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.