ArticleProceedings of the National Academy of Sciences of the United States of America2015
Mitochondrial retrograde signaling regulates neuronal function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 63 citations in OpenAlex.
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- Harnessing Metabolism to Combat Neurodegeneration: Strategies for Reversing Age-Related Cognitive Decline.ACS pharmacology & translational science · 2025Review
- Multi-target-directed therapeutic strategies for Alzheimer's disease: controlling amyloid-β aggregation, metal ion homeostasis, and enzyme inhibition.Chemical science · 2025Review
- NMNAT2 supports vesicular glycolysis via NAD homeostasis to fuel fast axonal transport.Molecular neurodegeneration · 2024Article
- Yeast NDI1 reconfigures neuronal metabolism and prevents the unfolded protein response in mitochondrial complex I deficiency.PLoS genetics · 2023Article
- Mitochondria in Cancer Stem Cells: From an Innocent Bystander to a Central Player in Therapy Resistance.Stem cells and cloning : advances and applications · 2023Review
- Germline TFAM levels regulate mitochondrial DNA copy number and mutant heteroplasmy inmicroPublication biology · 2023Article
- The Novel Role of Mitochondrial Citrate Synthase and Citrate in the Pathophysiology of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2023Review
- Role of OCT3 and DRP1 in the Transport of Paraquat in Astrocytes: A Mouse Study.Environmental health perspectives · 2022Article
- Mitochondrial DNA Transport in Drosophila Neurons.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Hippocampal Mitochondrial Transplantation Alleviates Age-Associated Cognitive Decline via Enhancing Wnt Signaling and Neurogenesis.Computational intelligence and neuroscience · 2022Article
- Mechanisms of Mitochondrial Malfunction in Alzheimer's Disease: New Therapeutic Hope.Oxidative medicine and cellular longevity · 2022Review
- Retrograde Mitochondrial Transport Is Essential for Organelle Distribution and Health in Zebrafish Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Targeting Age-Related Neurodegenerative Diseases by AAV-Mediated Gene Therapy.Advances in experimental medicine and biology · 2021Article
- Mitochondria: The Retina's Achilles' Heel in AMD.Advances in experimental medicine and biology · 2021Article
- The Evolutionary Conserved Transmembrane BAX Inhibitor Motif (TMBIM) Containing Protein Family Members 5 and 6 Are Essential for the Development and Survival ofFrontiers in cell and developmental biology · 2021Article
- Decoding the rosetta stone of mitonuclear communication.Pharmacological research · 2020Review
- Mitochondrial retrograde signalling in neurological disease.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Mitochondria are key regulators of cellular homeostasis, and mitochondrial dysfunction is strongly linked to neurodegenerative diseases, including Alzheimer's and Parkinson's. Mitochondria communicate their bioenergetic status to the cell via mitochondrial retrograde signaling. To investigate the role of mitochondrial retrograde signaling in neurons, we induced mitochondrial dysfunction in the Drosophila nervous system. Neuronal mitochondrial dysfunction causes reduced viability, defects in neuronal function, decreased redox potential, and reduced numbers of presynaptic mitochondria and active zones. We find that neuronal mitochondrial dysfunction stimulates a retrograde signaling response that controls the expression of several hundred nuclear genes. We show that the Drosophila hypoxia inducible factor alpha (HIFα) ortholog Similar (Sima) regulates the expression of several of these retrograde genes, suggesting that Sima mediates mitochondrial retrograde signaling. Remarkably, knockdown of Sima restores neuronal function without affecting the primary mitochondrial defect, demonstrating that mitochondrial retrograde signaling is partly responsible for neuronal dysfunction. Sima knockdown also restores function in a Drosophila model of the mitochondrial disease Leigh syndrome and in a Drosophila model of familial Parkinson's disease. Thus, mitochondrial retrograde signaling regulates neuronal activity and can be manipulated to enhance neuronal function, despite mitochondrial impairment.
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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.