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
刚刚
情怀应助EdmundLily采纳,获得10
1秒前
iNk驳回了Miller应助
1秒前
lzy完成签到,获得积分10
1秒前
Thi发布了新的文献求助10
2秒前
2秒前
xiaoyan发布了新的文献求助10
2秒前
陆啊陆发布了新的文献求助10
2秒前
李爱国应助朴素的天薇采纳,获得10
3秒前
4秒前
叮当猫完成签到,获得积分10
4秒前
奋斗魂幽完成签到 ,获得积分0
5秒前
囚徒发布了新的文献求助10
5秒前
5秒前
毛慢慢发布了新的文献求助10
6秒前
李哈发布了新的文献求助10
8秒前
en发布了新的文献求助10
8秒前
9秒前
求助萌新完成签到,获得积分10
10秒前
Li发布了新的文献求助10
10秒前
英姑应助囚徒采纳,获得10
10秒前
11秒前
173678完成签到,获得积分10
12秒前
MeetAgainLZH完成签到,获得积分10
12秒前
12秒前
13秒前
13秒前
roselin26发布了新的文献求助10
14秒前
李某某完成签到,获得积分10
15秒前
香蕉觅云应助毛慢慢采纳,获得10
16秒前
科研通AI2S应助光电效应采纳,获得10
16秒前
16秒前
16秒前
小布丁发布了新的文献求助10
17秒前
满载的船完成签到,获得积分10
17秒前
maaaaaa完成签到,获得积分10
17秒前
dududu应助小豆爱读书采纳,获得20
18秒前
gun去学习完成签到,获得积分10
18秒前
18秒前
闪闪采梦发布了新的文献求助10
18秒前
高分求助中
Evolution 10000
Sustainability in Tides Chemistry 2800
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
юрские динозавры восточного забайкалья 800
A new approach of magnetic circular dichroism to the electronic state analysis of intact photosynthetic pigments 500
Diagnostic immunohistochemistry : theranostic and genomic applications 6th Edition 500
Chen Hansheng: China’s Last Romantic Revolutionary 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 3148527
求助须知:如何正确求助?哪些是违规求助? 2799622
关于积分的说明 7836197
捐赠科研通 2457012
什么是DOI,文献DOI怎么找? 1307684
科研通“疑难数据库(出版商)”最低求助积分说明 628247
版权声明 601655