Diabetes Mellitus Disrupts LncRNA Malat1 Regulation of Cardiac Mitochondrial Genome-Encoded Protein Expression

马拉特1 线粒体 糖尿病性心肌病 生物 下调和上调 基因敲除 小RNA 线粒体DNA 细胞生物学 基因 分子生物学 心肌病 遗传学 长非编码RNA 内科学 医学 心力衰竭
作者
Andrew D. Taylor,Quincy A. Hathaway,Ethan Meadows,Andrya J. Durr,Amina Kunovac,Mark V. Pinti,Christopher C. H. Cook,Beth A. Miller,Remi Nohoesu,Roxy Nicoletti,Hafsat Olateju Alabere,Aaron R. Robart,John M. Hollander
出处
期刊:American Journal of Physiology-heart and Circulatory Physiology [American Physiological Society]
标识
DOI:10.1152/ajpheart.00607.2024
摘要

Understanding the cellular mechanisms behind diabetes-related cardiomyopathy is crucial as it is a common and deadly complication of diabetes mellitus. Dysregulation of the mitochondrial genome has been linked to diabetic cardiomyopathy, and can be ameliorated by altering microRNA (miRNA) availability in the mitochondrion. Long non-coding RNAs (lncRNAs) have been identified to downregulate miRNAs. This study aimed to determine if diabetes mellitus impacts the mitochondrial localization of lncRNAs, their interaction with miRNAs, and how this influences mitochondrial and cardiac function. In mouse and human non-diabetic and type 2 diabetic cardiac tissue, RNA was isolated from purified mitochondria and sequenced (Ilumina HiSeq). Malat1 was significantly downregulated in both human and mouse cardiac mitochondria. Use of a mouse model with an insertional deletion of Malat1 transcript expression resulted in exacerbated systolic and diastolic dysfunction when evaluated in conjunction with a high-fat diet. The cardiac effects of a high-fat diet were countered in a mouse model with transgenic overexpression of Malat1. MiR-320a, a miRNA that binds to both mitochondrial genome-encoded gene NADH-ubiquinone oxidoreductase chain 1 (MT-ND1) as well as Malat1, was upregulated in human and mouse diabetic mitochondria. Conversely, MT-ND1 was downregulated in human and mouse diabetic mitochondria. Mice with an insertional inactivation of Malat1 displayed increased recruitment of both miR-320a and MT-ND1 to the RNA-induced silencing complex (RISC). In vitro pulldown assays of Malat1 fragments with conserved secondary structure confirmed binding capacity for miR-320a. In vitro Seahorse assays indicated that Malat1 knockdown and miR-320a overexpression impaired overall mitochondrial bioenergetics and Complex I functionality. In summary, the disruption of Malat1 presence in mitochondria as observed in diabetic cardiomyopathy is linked to cardiac dysfunction and mitochondrial genome regulation.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
大碗牛肉面特辣完成签到 ,获得积分10
刚刚
晓山青发布了新的文献求助10
1秒前
希望天下0贩的0应助jiajia采纳,获得10
1秒前
好好发布了新的文献求助10
1秒前
evvj完成签到,获得积分10
3秒前
文艺鞋垫应助haha采纳,获得10
4秒前
脑洞疼应助haha采纳,获得10
4秒前
Ayla雁翎完成签到 ,获得积分10
5秒前
积极的珩发布了新的文献求助10
6秒前
洒脱鲲完成签到,获得积分10
7秒前
好好完成签到,获得积分10
7秒前
诚心水蓝完成签到,获得积分10
8秒前
8秒前
英俊的铭应助郁一刀采纳,获得10
8秒前
英俊的铭应助H恺采纳,获得10
9秒前
研白完成签到 ,获得积分10
11秒前
小蘑菇应助小鱼采纳,获得10
12秒前
14秒前
晓山青完成签到,获得积分10
18秒前
H恺发布了新的文献求助10
20秒前
123456发布了新的文献求助10
20秒前
21秒前
22秒前
深情安青应助称心的乘云采纳,获得10
23秒前
NexusExplorer应助陆扬采纳,获得20
23秒前
25秒前
26秒前
郁一刀发布了新的文献求助10
28秒前
小栗子完成签到 ,获得积分10
34秒前
研友_VZG7GZ应助积极的珩采纳,获得10
34秒前
WangSiya完成签到,获得积分10
35秒前
37秒前
37秒前
还好完成签到,获得积分10
39秒前
漂亮的毛巾完成签到,获得积分10
40秒前
陆扬发布了新的文献求助20
42秒前
小菜鸡发布了新的文献求助200
43秒前
44秒前
我是老大应助梦璃安采纳,获得10
44秒前
45秒前
高分求助中
中国国际图书贸易总公司40周年纪念文集 大事记1949-1987 2000
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
草地生态学 880
Threaded Harmony: A Sustainable Approach to Fashion 799
Basic Modern Theory of Linear Complex Analytic 𝑞-Difference Equations 510
Queer Politics in Times of New Authoritarianisms: Popular Culture in South Asia 500
Livre et militantisme : La Cité éditeur 1958-1967 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3058597
求助须知:如何正确求助?哪些是违规求助? 2714676
关于积分的说明 7441656
捐赠科研通 2360028
什么是DOI,文献DOI怎么找? 1250485
科研通“疑难数据库(出版商)”最低求助积分说明 607447
版权声明 596421