ArticlePloS one2009
Akt1 intramitochondrial cycling is a crucial step in the redox modulation of cell cycle progression.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 76 citations in OpenAlex.
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- Mitochondrial Signaling, the Mechanisms of AKI-to-CKD Transition and Potential Treatment Targets.International journal of molecular sciences · 2024Review
- Glyoxal-induced disruption of tumor cell progression in breast cancer.Molecular and clinical oncology · 2023Article
- Mitochondrial calcium exchange in physiology and disease.Physiological reviews · 2022Review
- Age-Related Oxidative Redox and Metabolic Changes Precede Intraneuronal Amyloid-β Accumulation and Plaque Deposition in a Transgenic Alzheimer's Disease Mouse Model.Journal of Alzheimer's disease : JAD · 2022Article
- An Integrated Transcriptomic Approach to Identify Molecular Markers of Calcineurin Inhibitor Nephrotoxicity in Pediatric Kidney Transplant Recipients.International journal of molecular sciences · 2021Article
- An evaluation of the molecular mode of action of trans-resveratrol in the Porphyromonas gingivalis lipopolysaccharide challenged neuronal cell model.Molecular biology reports · 2021Article
- Dual-Specific Protein and Lipid Phosphatase PTEN and Its Biological Functions.Cold Spring Harbor perspectives in medicine · 2020Review
- Mitochondrial Akt Signaling Modulated Reprogramming of Somatic Cells.Scientific reports · 2019Article
- Tetramethylpyrazine Analogue T-006 Exerts Neuroprotective Effects against 6-Hydroxydopamine-Induced Parkinson's DiseaseOxidative medicine and cellular longevity · 2019Article
- Phosphorylated Akt1 expression is associated with poor prognosis in cutaneous, oral and sinonasal melanomas.Oncotarget · 2018Article
- PTEN: Tumor Suppressor and Metabolic Regulator.Frontiers in endocrinology · 2018Review
- Subcellular distribution of ERK phosphorylation in tyrosine and threonine depends on redox status in murine lung cells.PloS one · 2018Article
- Cellular adaptation to xenobiotics: Interplay between xenosensors, reactive oxygen species and FOXO transcription factors.Redox biology · 2017Review
- Energy metabolism and inflammation in brain aging and Alzheimer's disease.Free radical biology & medicine · 2016Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
Akt is a serine/threonine kinase involved in cell proliferation, apoptosis, and glucose metabolism. Akt is differentially activated by growth factors and oxidative stress by sequential phosphorylation of Ser(473) by mTORC2 and Thr(308) by PDK1. On these bases, we investigated the mechanistic connection of H(2)O(2) yield, mitochondrial activation of Akt1 and cell cycle progression in NIH/3T3 cell line with confocal microscopy, in vivo imaging, and directed mutagenesis. We demonstrate that modulation by H(2)O(2) entails the entrance of cytosolic P-Akt1 Ser(473) to mitochondria, where it is further phosphorylated at Thr(308) by constitutive PDK1. Phosphorylation of Thr(308) in mitochondria determines Akt1 passage to nuclei and triggers genomic post-translational mechanisms for cell proliferation. At high H(2)O(2), Akt1-PDK1 association is disrupted and P-Akt1 Ser(473) accumulates in mitochondria in detriment to nuclear translocation; accordingly, Akt1 T308A is retained in mitochondria. Low Akt1 activity increases cytochrome c release to cytosol leading to apoptosis. As assessed by mass spectra, differential H(2)O(2) effects on Akt1-PDK interaction depend on the selective oxidation of Cys(310) to sulfenic or cysteic acids. These results indicate that Akt1 intramitochondrial-cycling is central for redox modulation of cell fate.
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Registered trials
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