ArticleThe Journal of biological chemistry2016
Forkhead Box O3A (FOXO3) and the Mitochondrial Disulfide Relay Carrier (CHCHD4) Regulate p53 Protein Nuclear Activity in Response to Exercise.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Mitochondrial innate immune signaling in skeletal muscle adaptation to exercise.Trends in endocrinology and metabolism: TEM · 2026Review
- CHCHD4 Oxidoreductase Activity: A Comprehensive Analysis of the Molecular, Functional, and Structural Properties of Its Redox-Regulated Substrates.Molecules (Basel, Switzerland) · 2025Review
- CHCHD4-TRIAP1 regulation of innate immune signaling mediates skeletal muscle adaptation to exercise.Cell reports · 2024Article
- Flow-induced endothelial mitochondrial remodeling mitigates mitochondrial reactive oxygen species production and promotes mitochondrial DNA integrity in a p53-dependent manner.Redox biology · 2022Article
- Regulation of p53 Function by Formation of Non-Nuclear Heterologous Protein Complexes.Biomolecules · 2022Review
- Transcription Factor Movement and Exercise-Induced Mitochondrial Biogenesis in Human Skeletal Muscle: Current Knowledge and Future Perspectives.International journal of molecular sciences · 2022Review
- Impact of Nutrition on Short-Term Exercise-Induced Sirtuin Regulation: Vegans Differ from Omnivores and Lacto-Ovo Vegetarians.Nutrients · 2020Article
- Exercise is mitochondrial medicine for muscle.Sports medicine and health science · 2019Review
- p53 prevents doxorubicin cardiotoxicity independently of its prototypical tumor suppressor activities.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- The Role of p53 in Determining Mitochondrial Adaptations to Endurance Training in Skeletal Muscle.Scientific reports · 2018Article
- Principles of Exercise Prescription, and How They Influence Exercise-Induced Changes of Transcription Factors and Other Regulators of Mitochondrial Biogenesis.Sports medicine (Auckland, N.Z.) · 2018Review
- The mitochondrial oxidoreductase CHCHD4 is present in a semi-oxidized state in vivo.Redox biology · 2018Article
- FGF1 induces resistance to chemotherapy in ovarian granulosa tumor cells through regulation of p53 mitochondrial localization.Oncogenesis · 2018Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Although exercise is linked with improved health, the specific molecular mechanisms underlying its various benefits require further clarification. Here we report that exercise increases the nuclear localization and activity of p53 by acutely down-regulating coiled-coil-helix-coiled-coil-helix domain 4 (CHCHD4), a carrier protein that mediates p53 import into the mitochondria. This response to exercise is lost in transgenic mice with constitutive expression of CHCHD4. Mechanistically, exercise-induced nuclear transcription factor FOXO3 binds to the CHCHD4 promoter and represses its expression, preventing the translocation of p53 to the mitochondria and thereby increasing p53 nuclear localization. The synergistic increase in nuclear p53 and FOXO3 by exercise can facilitate their known interaction in transactivating Sirtuin 1 (SIRT1), a NAD
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