ArticleJournal of molecular and cellular cardiology2018
Mitochondrial proteome disruption in the diabetic heart through targeted epigenetic regulation at the mitochondrial heat shock protein 70 (mtHsp70) nuclear locus.
Article in Journal of molecular and cellular cardiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Targeting mitochondrial quality control in diabetic kidney disease: emerging therapeutic opportunities.Renal failure · 2026Review
- Dusp15 modulates mtHsp70 Thr116 phosphorylation state to preserve mito-UPR and attenuate cardiac dysfunction in diabetic cardiomyopathy.Cardiovascular diabetology · 2026Article
- Dysregulated inflammation, oxidative stress, and protein quality control in diabetic HFpEF: unraveling mechanisms and therapeutic targets.Cardiovascular diabetology · 2025Article
- Enhancement of Mitochondrial Homeostasis: A Novel Approach to Attenuate Hypoxic Myocardial Injury.International journal of medical sciences · 2024Review
- Diabetes-induced chronic heart failure is due to defects in calcium transporting and regulatory contractile proteins: cellular and molecular evidence.Heart failure reviews · 2023Review
- Grpel2 maintains cardiomyocyte survival in diabetic cardiomyopathy through DLST-mediated mitochondrial dysfunction: a proof-of-concept study.Journal of translational medicine · 2023Article
- Genomic, Proteomic, and Metabolic Comparisons of Small Animal Models of Heart Failure With Preserved Ejection Fraction: A Tale of Mice, Rats, and Cats.Journal of the American Heart Association · 2022Review
- Review
- Transcriptomics of single dose and repeated carbon black and ozone inhalation co-exposure highlight progressive pulmonary mitochondrial dysfunction.Particle and fibre toxicology · 2021Article
- Mitochondrial Chaperones and Proteases in Cardiomyocytes and Heart Failure.Frontiers in molecular biosciences · 2021Review
- Role of the Mitochondrial Protein Import Machinery and Protein Processing in Heart Disease.Frontiers in cardiovascular medicine · 2021Review
- Tom70 protects against diabetic cardiomyopathy through its antioxidant and antiapoptotic properties.Hypertension research : official journal of the Japanese Society of Hypertension · 2020Article
- Cellular Protein Quality Control in Diabetic Cardiomyopathy: From Bench to Bedside.Frontiers in cardiovascular medicine · 2020Review
- Molecular Perspectives of Mitochondrial Adaptations and Their Role in Cardiac Proteostasis.Frontiers in physiology · 2020Review
- Machine-learning to stratify diabetic patients using novel cardiac biomarkers and integrative genomics.Cardiovascular diabetology · 2019Article
- Mitochondrial dysfunction in type 2 diabetes mellitus: an organ-based analysis.American journal of physiology. Endocrinology and metabolism · 2019Review
- Diabetic Cardiomyopathy: Current and Future Therapies. Beyond Glycemic Control.Frontiers in physiology · 2018Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
>99% of the mitochondrial proteome is nuclear-encoded. The mitochondrion relies on a coordinated multi-complex process for nuclear genome-encoded mitochondrial protein import. Mitochondrial heat shock protein 70 (mtHsp70) is a key component of this process and a central constituent of the protein import motor. Type 2 diabetes mellitus (T2DM) disrupts mitochondrial proteomic signature which is associated with decreased protein import efficiency. The goal of this study was to manipulate the mitochondrial protein import process through targeted restoration of mtHsp70, in an effort to restore proteomic signature and mitochondrial function in the T2DM heart. A novel line of cardiac-specific mtHsp70 transgenic mice on the db/db background were generated and cardiac mitochondrial subpopulations were isolated with proteomic evaluation and mitochondrial function assessed. MicroRNA and epigenetic regulation of the mtHsp70 gene during T2DM were also evaluated. MtHsp70 overexpression restored cardiac function and nuclear-encoded mitochondrial protein import, contributing to a beneficial impact on proteome signature and enhanced mitochondrial function during T2DM. Further, transcriptional repression at the mtHsp70 genomic locus through increased localization of H3K27me3 during T2DM insult was observed. Our results suggest that restoration of a key protein import constituent, mtHsp70, provides therapeutic benefit through attenuation of mitochondrial and contractile dysfunction in T2DM.
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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.