ArticleAging cell2020
Corrupted ER-mitochondrial calcium homeostasis promotes the collapse of proteostasis.
Article in Aging cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Regulation of autophagy, lipid metabolism, and neurodegenerative pathology by heparan sulfate proteoglycans.Frontiers in genetics · 2022Pooled it
- Calcium signaling hypothesis: A non-negligible pathogenesis in Alzheimer's disease.Journal of advanced research · 2025Review
- Presenilin Loss Impairs Synaptic Transmission and Causes Axonal Degeneration through Ryanodine Receptor Dysfunction, Independent of γ-Secretase Activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Identification of presenilin mutations that have sufficient gamma-secretase proteolytic activity to mediate Notch signaling but disrupt organelle and neuronal health.Neurobiology of disease · 2025Article
- C. elegans Presenilin Mediates Inter-Organelle Contacts and Communication that Is Required for Lysosome Activity.Aging and disease · 2024Article
- Article
- Deregulation of Mitochondrial Calcium Handling Due to Presenilin Loss Disrupts Redox Homeostasis and Promotes Neuronal Dysfunction.Antioxidants (Basel, Switzerland) · 2022Article
- Impact of Exercise and Aging on Mitochondrial Homeostasis in Skeletal Muscle: Roles of ROS and Epigenetics.Cells · 2022Review
- Modeling Alzheimer's Disease inBiomedicines · 2022Review
- Increased mitochondrial calcium uptake and concomitant mitochondrial activity by presenilin loss promotes mTORC1 signaling to drive neurodegeneration.Aging cell · 2021Article
- Plant Mitophagy in Comparison to Mammals: What Is Still Missing?International journal of molecular sciences · 2021Review
- Oxidative stress and redox signaling in CRPC progression: therapeutic potential of clinically-tested Nrf2-activators.Cancer drug resistance (Alhambra, Calif.) · 2021Review
- The Role of Mitochondrial Calcium Homeostasis in Alzheimer's and Related Diseases.International journal of molecular sciences · 2020Review
- Interrelation between ROS and CaRedox biology · 2020Review
- The Role of CaCells · 2020Review
- Corrupted ER-mitochondrial calcium homeostasis promotes the collapse of proteostasis.Aging cell · 2020Article
- Nanoliposomes as a Therapeutic Tool for Alzheimer's Disease.Frontiers in synaptic neuroscience · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Aging and age-related diseases are associated with a decline of protein homeostasis (proteostasis), but the mechanisms underlying this decline are not clear. In particular, decreased proteostasis is a widespread molecular feature of neurodegenerative diseases, such as Alzheimer's disease (AD). Familial AD is largely caused by mutations in the presenilin encoding genes; however, their role in AD is not understood. In this study, we investigate the role of presenilins in proteostasis using the model system Caenorhabditis elegans. Previously, we found that mutations in C. elegans presenilin cause elevated ER to mitochondria calcium signaling, which leads to an increase in mitochondrial generated oxidative stress. This, in turn, promotes neurodegeneration. To understand the cellular mechanisms driving neurodegeneration, using several molecular readouts of protein stability in C. elegans, we find that presenilin mutants have widespread defects in proteostasis. Markedly, we demonstrate that these defects are independent of the protease activity of presenilin and that reduction in ER to mitochondrial calcium signaling can significantly prevent the proteostasis defects observed in presenilin mutants. Furthermore, we show that supplementing presenilin mutants with antioxidants suppresses the proteostasis defects. Our findings indicate that defective ER to mitochondria calcium signaling promotes proteostatic collapse in presenilin mutants by increasing oxidative stress.
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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.