Increased Drp1 acetylation by lipid overload induces cardiomyocyte death and heart dysfunction
Data files
Jan 16, 2024 version files 1.06 MB
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Figure_1_source_data.xlsx
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Figure_2_source_data.xlsx
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Figure_3_source_data.xlsx
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Figure_4_source_data.xlsx
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Figure_5_source_data.xlsx
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Figure_6_source_data.xlsx
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Figure_7_source_data.xlsx
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Figure_8_source_data.xlsx
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Online_Figure_I_source_data.xlsx
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Online_Figure_II_source_data.xlsx
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Online_Figure_III_source_data.xlsx
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Online_Figure_IV_source_data.xlsx
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Online_Figure_V_source_data.xlsx
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Online_Figure_VI_source_data.xlsx
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Online_Figure_VII_source_data.xlsx
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Online_Figure_VIII_source_data.xlsx
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Online_Tables_1-2_source_data.xlsx
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Raw_WB_images_for_Fig_1-8_S2_S6___S7.pdf
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README.md
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README.txt
Abstract
Metabolic syndrome is a cluster of abnormalities characterized by obesity and insulin resistance, which compromise energy metabolism, damage mitochondria, cause cardiomyocyte death, and eventually impair heart contraction and relaxation performance. Despite the increasing prevalence of heart complications in obese and diabetic patients, our knowledge on how obese and diabetes mellitus impair heart function is very limited. In this study, we used animal and cell culture models in rodents or monkeys and generated lipid overload models to mimic obesity conditions. We found that excessive lipid supply decreased nicotinamide adenine dinucleotide (oxidized) levels and increased the acetylation of a fission protein Drp1 at a specific lysine residue (K642). Drp1 acetylation at K642 activated Drp1 through phosphorylation, mitochondrial translocation, and oligomerization. The excessively activated Drp1 had higher GTPase activity, bound with VDAC1 on mitochondria, induced mitochondrial fission, and caused cardiomyocyte death. These findings provide new information regarding how lipid overload regulates redox environment, protein acetylation, and the function of mitochondrial fission protein Drp1 in the heart.
README
This README file was generated on 2023-01-10 by Wang Wang.
I. GENERAL INFORMATION
Title of dataset: Increased Drp1 Acetylation by Lipid Overload Induces Cardiomyocyte Death and Heart Dysfunction
Access this dataset on dryad: http://doi:10.5061/dryad.zs7h44jgw
Abstract: Metabolic syndrome is a cluster of abnormalities characterized by obesity and insulin resistance, which compromise energy metabolism, damage mitochondria, cause cardiomyocyte death, and eventually impair heart contraction and relaxation performance. Despite the increasing prevalence of heart complications in obese and diabetic patients, our knowledge on how obese and diabetes mellitus impair heart function is very limited. In this study, we used animal and cell culture models in rodents or monkeys and generated lipid overload models to mimic obesity conditions. We found that excessive lipid supply decreased nicotinamide adenine dinucleotide (oxidized) levels and increased the acetylation of a fission protein Drp1 at a specific lysine residue (K642). Drp1 acetylation at K642 activated Drp1 through phosphorylation, mitochondrial translocation, and oligomerization. The excessively activated Drp1 had higher GTPase activity, bound with VDAC1 on mitochondria, induced mitochondrial fission, and caused cardiomyocyte death. These findings provide new information regarding how lipid overload regulates redox environment, protein acetylation, and the function of mitochondrial fission protein Drp1 in the heart.
Principal investigator contact information: Wang Wang, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle WA USA. Email: wangwang@uw.edu
Date of data collection: 2018-2020
Geographic location of data collection: University of Washington, Seattle, WA USA
Funding sources that supported the collection of the data:
(1) National Institutes of Health awards: HL114760, HL110349, HL137266, HL093671 and HL142864
(2) American Heart Association awards: 18EIA33900041 and 19CDA34660311
(3) National Institute on Aging (NIA) Intramural Research ProgramDataset contents
(1) Figure 1 source data.xlsx
(2) Figure 2 source data.xlsx
(3) Figure 3 source data.xlsx
(4) Figure 4 source data.xlsx
(5) Figure 5 source data.xlsx
(6) Figure 6 source data.xlsx
(7) Figure 7 source data.xlsx
(8) Figure 8 source data.xlsx
(9) Online Figure I source data.xlsx
(10) Online Figure II source data.xlsx
(11) Online Figure III source data.xlsx
(12) Online Figure IV source data.xlsx
(13) Online Figure V source data.xlsx
(14) Online Figure VI source data.xlsx
(15) Online Figure VII source data.xlsx
(16) Online Figure VIII source data.xlsx
(17) Online Tables 1-2 source data.xlsx
(18) Raw WB images for Fig 1-8 S2 S6 & S7.pdf
II. DESCRIPTION OF THE DATA AND FILE STRUCTURE
All source data and raw Western Blotting (WB) images corresponding to research paper "Increased Drp1 Acetylation by Lipid Overload Induces Cardiomyocyte Death and Heart Dysfunction" published in Circulation Research. Methods are described in detail in the online supplemental materials of this paper.
The Excel files contain source data for the bar graphs of Figures 1-8, Online Figures I-VIII and Online Tables 1-2 of this paper. For clarity, each spreadsheet is labeled with its location (figure/panel) in the paper. The first cell in each spreadsheet contains a briefly description of the contents.
The pdf file named: Raw WB images for Fig 1-8 S2 S6 & S7.pdf contains all the raw WB images in this paper, including images in Figures 1-8 and Online Figures II, VI, and VII. In some images, red rectangles are used to highlight the portion of the image used in the paper.
III. SHARING/ACCESS INFORMATION
Links to other publicly accessible locations of the data: Hu Q, Zhang H, Gutierrez Cortes N, Wu D, Wang P, Zhang J, Mattison JA, Smith E, Bettcher LF, Wang M, Lakatta EG, Sheu SS and Wang W. Increased Drp1 Acetylation by Lipid Overload Induces Cardiomyocyte Death and Heart Dysfunction. Circulation research. 2020;126:456-470.
https://doi.org/10.1161/CIRCRESAHA.119.315252Recommended citation for this dataset: Wang Wang (2024). Data from: Increased Drp1 Acetylation by Lipid Overload Induces Cardiomyocyte Death and Heart Dysfunction. Dryad Digital Repository. https://doi:10.5061/dryad.zs7h44jgw
Methods
1. All source data and raw Western Blotting (WB) images corresponding to the research paper 'Increased Drp1 Acetylation by Lipid Overload Induces Cardiomyocyte Death and Heart Dysfunction’ published in Circulation Research. Methods are described in detail in the online supplemental materials of this paper.
2. The Excel files contain source data for the bar graphs of Figures 1–8, Online Figures I–VIII and Online Tables 1–2 of this paper. For clarity, each spreadsheet is labeled with its location (figure/panel) in the paper. The first cell in each spreadsheet contains a brief description of the contents.
3. The pdf file named: Raw WB images for Fig 1–8 S2 S6 & S7.pdf contains all the raw WB images in this paper, including images in Figures 1-8 and Online Figures II, VI, and VII. In some images, red rectangles are used to highlight the portion of the image used in the paper.