ArticleThe EMBO journal2018
A novel lysosome-to-mitochondria signaling pathway disrupted by amyloid-β oligomers.
Article in The EMBO journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Inter-organellar Communication in Parkinson's and Alzheimer's Disease: Looking Beyond Endoplasmic Reticulum-Mitochondria Contact Sites.Frontiers in neuroscience · 2022Pooled it
- Metabolism and oxygen tension in Alzheimer's disease mouse model using two-photon FLIM-PLIM microscopy.Neurophotonics · 2026Article
- Mitochondrial NADK2-dependent NADPH controls tau oligomer uptake in human neurons.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Endogenously generated Dutch-type Aβ non-fibrillar aggregates dysregulate presynaptic neurotransmission in the absence of detectable inflammation.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Unraveling GDAP1: Bridging Mitochondrial Biology and Peripheral Neuropathy.Biomolecules · 2026Review
- Mitochondrial dysfunction in Alzheimer's disease: connecting pathophysiology with neuroimaging.Frontiers in aging neuroscience · 2026Review
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Failure of lysosomal acidification and endomembrane network in neurodegeneration.Experimental & molecular medicine · 2025Review
- Bioenergetic failure and oxidative stress: mitochondrial contributions to Alzheimer's disease.Inflammopharmacology · 2025Review
- Label-free metabolic fingerprinting of motile mammalian spermatozoa with subcellular resolution.BMC biology · 2025Article
- Microglia degrade Alzheimer's amyloid-beta deposits extracellularly via digestive exophagy.Cell reports · 2024Article
- Disrupted mitochondrial response to nutrients is a presymptomatic event in the cortex of the APPAlzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies.Signal transduction and targeted therapy · 2024Review
- Dysregulation of mTOR by tau in Alzheimer's disease.Cytoskeleton (Hoboken, N.J.) · 2024Review
- Mitochondria-sequestered Aβ renders synaptic mitochondria vulnerable in the elderly with a risk of Alzheimer disease.JCI insight · 2023Article
- Characterization of mitochondrial dysfunction due to laser damage by 2-photon FLIM microscopy.Scientific reports · 2022Article
- SOD1 mediates lysosome-to-mitochondria communication and its dysregulation by amyloid-β oligomers.Neurobiology of disease · 2022Article
- Transcriptome and Translatome Regulation of Pathogenesis in Alzheimer's Disease Model Mice.Journal of Alzheimer's disease : JAD · 2022Article
- Based on molecular structures: Amyloid-β generation, clearance, toxicity and therapeutic strategies.Frontiers in molecular neuroscience · 2022Review
- Mitochondria inter-organelle relationships in cancer protein aggregation.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
The mechanisms of mitochondrial dysfunction in Alzheimer's disease are incompletely understood. Using two-photon fluorescence lifetime microscopy of the coenzymes, NADH and NADPH, and tracking brain oxygen metabolism with multi-parametric photoacoustic microscopy, we show that activation of lysosomal mechanistic target of rapamycin complex 1 (mTORC1) by insulin or amino acids stimulates mitochondrial activity and regulates mitochondrial DNA synthesis in neurons. Amyloid-β oligomers, which are precursors of amyloid plaques in Alzheimer's disease brain and stimulate mTORC1 protein kinase activity at the plasma membrane but not at lysosomes, block this Nutrient-induced Mitochondrial Activity (NiMA) by a mechanism dependent on tau, which forms neurofibrillary tangles in Alzheimer's disease brain. NiMA was also disrupted in fibroblasts derived from two patients with tuberous sclerosis complex, a genetic disorder that causes dysregulation of lysosomal mTORC1. Thus, lysosomal mTORC1 couples nutrient availability to mitochondrial activity and links mitochondrial dysfunction to Alzheimer's disease by a mechanism dependent on the soluble building blocks of the poorly soluble plaques and tangles.
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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.