ArticleActa neuropathologica2022
A CHCHD6-APP axis connects amyloid and mitochondrial pathology in Alzheimer's disease.
Article in Acta neuropathologica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Patient cerebral organoids capture Alzheimer's disease proteomic biomarkers and drug targets.bioRxiv : the preprint server for biology · 2026Article
- TDP-43 impairs glycolysis by sequestering hexokinase 1 in amyotrophic lateral sclerosis.Acta neuropathologica · 2026Article
- The role of MICOS in modulating mitochondrial dynamics and structural changes in vulnerable regions of Alzheimer's Disease.bioRxiv : the preprint server for biology · 2025Article
- PI3K/AKT/GSK3β regulatory axis in bone mesenchymal stem cells initiates diabetic myocardial infarctionWorld journal of experimental medicine · 2025Article
- Structures and functions of the MICOS: Pathogenesis and therapeutic implications in Alzheimer's disease.Acta pharmaceutica Sinica. B · 2025Review
- CHCHD4 Oxidoreductase Activity: A Comprehensive Analysis of the Molecular, Functional, and Structural Properties of Its Redox-Regulated Substrates.Molecules (Basel, Switzerland) · 2025Review
- Mitochondrial dysfunction in Alzheimer's disease: Guiding the path to targeted therapies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- The AICD interactome: implications in neurodevelopment and neurodegeneration.Biochemical Society transactions · 2024Review
- Heritable Risk and Protective Genetic Components of Glaucoma Medication Non-Adherence.International journal of molecular sciences · 2023Article
- Interactions between amyloid, amyloid precursor protein, and mitochondria.Biochemical Society transactions · 2023Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
The mechanistic relationship between amyloid-beta precursor protein (APP) processing and mitochondrial dysfunction in Alzheimer's disease (AD) has long eluded the field. Here, we report that coiled-coil-helix-coiled-coil-helix domain containing 6 (CHCHD6), a core protein of the mammalian mitochondrial contact site and cristae organizing system, mechanistically connects these AD features through a circular feedback loop that lowers CHCHD6 and raises APP processing. In cellular and animal AD models and human AD brains, the APP intracellular domain fragment inhibits CHCHD6 transcription by binding its promoter. CHCHD6 and APP bind and stabilize one another. Reduced CHCHD6 enhances APP accumulation on mitochondria-associated ER membranes and accelerates APP processing, and induces mitochondrial dysfunction and neuronal cholesterol accumulation, promoting amyloid pathology. Compensation for CHCHD6 loss in an AD mouse model reduces AD-associated neuropathology and cognitive impairment. Thus, CHCHD6 connects APP processing and mitochondrial dysfunction in AD. This provides a potential new therapeutic target for patients.
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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.