ArticleThe Journal of clinical investigation2015
Kruppel-like factor 4 is critical for transcriptional control of cardiac mitochondrial homeostasis.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 137 citations in OpenAlex.
- KLF4/MLL3 complex axis drives NRBP2 transcription to eliminate acute myeloid leukemia cells.Leukemia · 2026Article
- KLF4 in Parkinson's Disease: Decoding the Molecular Puzzle of Neuroinflammation, Oxidative Stress, and Emerging Therapies.Current medical science · 2026Review
- Endothelial KLF4 depletion drives age-related neurovascular dysfunction and neuropsychiatric impairment.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Dapagliflozin alleviates sunitinib-induced cardiotoxicity through AMPKα-PPARα axis and enhances the sensitivity of renal cell carcinoma to sunitinib.BMC medicine · 2025Article
- Integrative multi-omics uncovers skeletal muscle enhancer programming of cardiorespiratory fitness.bioRxiv : the preprint server for biology · 2025Article
- Impacts of aging and fluid shear stress on vascular endothelial metabolism and atherosclerosis development.Journal of biomedical science · 2025Review
- FNDC4 Prevents Aging-Related Cardiac Dysfunction: By Restoring AMPKα/PPARα-Dependent Mitochondrial Function.JACC. Basic to translational science · 2025Article
- Gene therapy prevents onset of mitochondrial cardiomyopathy in neonatal mice with Ndufs6 deficiency.Cell death discovery · 2025Article
- Screening of biomarkers for diagnosing chronic kidney disease and heart failure with preserved ejection fraction through bioinformatics analysis.Biochemistry and biophysics reports · 2025Article
- Childhood triglyceride-glucose index and pre-hypertension in adulthood: a prospective cohort study.Frontiers in endocrinology · 2025Article
- Krüppel-like factors in mitochondrial quality control.Frontiers in physiology · 2025Review
- Klf9 is essential for cardiac mitochondrial homeostasis.Nature cardiovascular research · 2024Article
- Myostatin regulates energy homeostasis through autocrine- and paracrine-mediated microenvironment communication.The Journal of clinical investigation · 2024Article
- Hypertriglyceridemia: Molecular and Genetic Landscapes.International journal of molecular sciences · 2024Review
- KLF transcription factors in bone diseases.Journal of cellular and molecular medicine · 2024Review
- Cardiac maturation.Journal of molecular and cellular cardiology · 2024Review
- Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function.Circulation · 2024Article
- KLF4 facilitates chromatin accessibility remodeling in porcine early embryos.Science China. Life sciences · 2024Article
- The SIRT3-ATAD3A axis regulates MAM dynamics and mitochondrial calcium homeostasis in cardiac hypertrophy.International journal of biological sciences · 2024Article
- Krüpple-like factors in cardiomyopathy: emerging player and therapeutic opportunities.Frontiers in cardiovascular medicine · 2024Review
20 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 7 institutions in 2 countries.
Funding
Abstract
Mitochondrial homeostasis is critical for tissue health, and mitochondrial dysfunction contributes to numerous diseases, including heart failure. Here, we have shown that the transcription factor Kruppel-like factor 4 (KLF4) governs mitochondrial biogenesis, metabolic function, dynamics, and autophagic clearance. Adult mice with cardiac-specific Klf4 deficiency developed cardiac dysfunction with aging or in response to pressure overload that was characterized by reduced myocardial ATP levels, elevated ROS, and marked alterations in mitochondrial shape, size, ultrastructure, and alignment. Evaluation of mitochondria isolated from KLF4-deficient hearts revealed a reduced respiration rate that is likely due to defects in electron transport chain complex I. Further, cardiac-specific, embryonic Klf4 deletion resulted in postnatal premature mortality, impaired mitochondrial biogenesis, and altered mitochondrial maturation. We determined that KLF4 binds to, cooperates with, and is requisite for optimal function of the estrogen-related receptor/PPARγ coactivator 1 (ERR/PGC-1) transcriptional regulatory module on metabolic and mitochondrial targets. Finally, we found that KLF4 regulates autophagy flux through transcriptional regulation of a broad array of autophagy genes in cardiomyocytes. Collectively, these findings identify KLF4 as a nodal transcriptional regulator of mitochondrial homeostasis.
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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.