ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2021
Proteomic analysis of mitochondrial biogenesis in cardiomyocytes differentiated from human induced pluripotent stem cells.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Using human induced pluripotent stem cell-derived cardiomyocytes to understand the mechanisms driving cardiomyocyte maturation.Frontiers in cardiovascular medicine · 2022Pooled it
- Impact of maternal lipopolysaccharide and polyinosinic-polycytidylic acid-induced infections on offspring cardiac development: Mitochondrial dysfunction and metabolic alterations.Genes & diseases · 2026Article
- Disturbed mitochondrial maturation in cardiolipin remodeling-deficient cardiomyocytes.iScience · 2026Article
- Engineering Mitochondrial Biogenesis in iPSC-CMs: CRISPR-Guided Approaches for Advanced Cardiomyocyte Development.Journal of cardiovascular development and disease · 2026Review
- Role of LONP1 in human diseases: molecular mechanisms and therapeutic potential.Cellular & molecular biology letters · 2026Review
- Induced Pluripotent Stem Cells in Cardiomyopathy: Advancing Disease Modeling, Therapeutic Development, and Regenerative Therapy.International journal of molecular sciences · 2025Review
- Mitochondrial metabolic maturation in postnatal right ventricle restricted by volume overload.Intractable & rare diseases research · 2025Article
- TRIM21-mediated ubiquitination of SQSTM1/p62 abolishes its Ser403 phosphorylation and enhances palmitic acid cytotoxicity.Autophagy · 2025Article
- Data-Driven Maturity Level Evaluation for Cardiomyocytes Derived from Human Pluripotent Stem Cells (Invited Paper).Electronics · 2024Article
- Maturation of pluripotent stem cell-derived cardiomyocytes: limitations and challenges from metabolic aspects.Stem cell research & therapy · 2024Review
- Proteomics of the heart.Physiological reviews · 2024Review
- Down-regulation of Lon protease 1 lysine crotonylation aggravates mitochondrial dysfunction in polycystic ovary syndrome.MedComm · 2023Article
- AKAP1 Regulates Mitochondrial Dynamics during the Fatty-Acid-Promoted Maturation of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes as Indicated by Proteomics Sequencing.International journal of molecular sciences · 2023Article
- Energy substrate metabolism and oxidative stress in metabolic cardiomyopathy.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Roles of LonP1 in Oral-Maxillofacial Developmental Defects and Tumors: A Novel Insight.International journal of molecular sciences · 2022Review
- iPSC-derived cranial neural crest-like cells can replicate dental pulp tissue with the aid of angiogenic hydrogel.Bioactive materials · 2022Article
- Human induced pluripotent stem cells for studying mitochondrial diseases in the heart.FEBS letters · 2022Review
- IDH2-mediated regulation of the biogenesis of the oxidative phosphorylation system.Science advances · 2022Article
- Energy Metabolism on Mitochondrial Maturation and Its Effects on Cardiomyocyte Cell Fate.Frontiers in cell and developmental biology · 2022Review
- Dissecting the concordant and disparate roles of NDUFAF3 and NDUFAF4 in mitochondrial complex I biogenesis.iScience · 2021Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Mitochondria play key roles in the differentiation and maturation of human cardiomyocytes (CMs). As human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold potential in the treatment of heart diseases, we sought to identify key mitochondrial pathways and regulators, which may provide targets for improving cardiac differentiation and maturation. Proteomic analysis was performed on enriched mitochondrial protein extracts isolated from hiPSC-CMs differentiated from dermal fibroblasts (dFCM) and cardiac fibroblasts (cFCM) at time points between 12 and 115 days of differentiation, and from adult and neonatal mouse hearts. Mitochondrial proteins with a twofold change at time points up to 120 days relative to 12 days were subjected to ingenuity pathway analysis (IPA). The highest upregulation was in metabolic pathways for fatty acid oxidation (FAO), the tricarboxylic acid (TCA) cycle, oxidative phosphorylation (OXPHOS), and branched chain amino acid (BCAA) degradation. The top upstream regulators predicted to be activated were peroxisome proliferator-activated receptor γ coactivator 1 α (PGC1-α), the insulin receptor (IR), and the retinoblastoma protein (Rb1) transcriptional repressor. IPA and immunoblotting showed upregulation of the mitochondrial LonP1 protease-a regulator of mitochondrial proteostasis, energetics, and metabolism. LonP1 knockdown increased FAO in neonatal rat ventricular cardiomyocytes (nRVMs). Our results support the notion that LonP1 upregulation negatively regulates FAO in cardiomyocytes to calibrate the flux between glucose and fatty acid oxidation. We discuss potential mechanisms by which IR, Rb1, and LonP1 regulate the metabolic shift from glycolysis to OXPHOS and FAO. These newly identified factors and pathways may help in optimizing the maturation of iPSC-CMs.
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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 Socratic graph.