DOI: 10.5061/dryad.zs7h44jgw
title: Increased Drp1 acetylation by lipid overload induces cardiomyocyte death and heart dysfunction

description: 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.
description: 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.
description: This README file was generated on 2023-01-10 by Wang Wang. I. GENERAL
 INFORMATION 1. Title of dataset: Increased Drp1 Acetylation by Lipid
 Overload Induces Cardiomyocyte Death and Heart Dysfunction 2. Access this
 dataset on dryad: 3. 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. 4. Principal investigator contact information: Wang Wang,
 Department of Anesthesiology and Pain Medicine, University of Washington,
 Seattle WA USA. Email: 5. Date of data collection:
 2018-2020 6. Geographic location of data collection: University of
 Washington, Seattle, WA USA 7. 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 Program 8. Dataset 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 1. 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. 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 briefly
 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. III. SHARING/ACCESS INFORMATION 1. 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.
 2. Recommended
 citation for this dataset: Wang Wang (2024). Data from: Increased Drp1
 Acetylation by Lipid Overload Induces Cardiomyocyte Death and Heart
 Dysfunction. Dryad Digital Repository.