Your browser doesn't support javascript.
loading
Mitochondrial long non-coding RNA GAS5 tunes TCA metabolism in response to nutrient stress.
Sang, Lingjie; Ju, Huai-Qiang; Yang, Zuozhen; Ge, Qiwei; Zhang, Zhen; Liu, Fangzhou; Yang, Luojia; Gong, Hangdi; Shi, Chengyu; Qu, Lei; Chen, Hui; Wu, Minjie; Chen, Hao; Li, Ruihua; Zhuang, Qianqian; Piao, Hailong; Yan, Qingfeng; Yu, Weishi; Wang, Liangjing; Shao, Jianzhong; Liu, Jian; Wang, Wenqi; Zhou, Tianhua; Lin, Aifu.
Affiliation
  • Sang L; MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, China.
  • Ju HQ; Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
  • Yang Z; MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, China.
  • Ge Q; MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, China.
  • Zhang Z; Department of Gastroenterology, The Second Affiliated Hospital, School of Medicine and Institute of Gastroenterology, Zhejiang University, Hangzhou, China.
  • Liu F; MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, China.
  • Yang L; MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, China.
  • Gong H; MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, China.
  • Shi C; MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, China.
  • Qu L; MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, China.
  • Chen H; MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, China.
  • Wu M; MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, China.
  • Chen H; MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, China.
  • Li R; MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, China.
  • Zhuang Q; MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, China.
  • Piao H; MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, China.
  • Yan Q; CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Liaoning, China.
  • Yu W; MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, China.
  • Wang L; Cipher Gene, Beijing, China.
  • Shao J; Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
  • Liu J; Department of Gastroenterology, The Second Affiliated Hospital, School of Medicine and Institute of Gastroenterology, Zhejiang University, Hangzhou, China.
  • Wang W; MOE Laboratory of Biosystem Homeostasis and Protection, College of Life Sciences, Zhejiang University, Hangzhou, China.
  • Zhou T; Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, International Campus, Zhejiang University, Haining, China.
  • Lin A; Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.
Nat Metab ; 3(1): 90-106, 2021 01.
Article in En | MEDLINE | ID: mdl-33398195
ABSTRACT
Organelles use specialized molecules to regulate their essential cellular processes. However, systematically elucidating the subcellular distribution and function of molecules such as long non-coding RNAs (lncRNAs) in cellular homeostasis and diseases has not been fully achieved. Here, we reveal the diverse and abundant subcellular distribution of organelle-associated lncRNAs from mitochondria, lysosomes and endoplasmic reticulum. Among them, we identify the mitochondrially localized lncRNA growth-arrest-specific 5 (GAS5) as a tumour suppressor in maintaining cellular energy homeostasis. Mechanistically, energy-stress-induced GAS5 modulates mitochondrial tricarboxylic acid flux by disrupting metabolic enzyme tandem association of fumarate hydratase, malate dehydrogenase and citrate synthase, the canonical members of the tricarboxylic acid cycle. GAS5 negatively correlates with levels of its associated mitochondrial metabolic enzymes in tumours and benefits overall survival in individuals with breast cancer. Together, our detailed annotation of subcellular lncRNA distribution identifies a functional role for lncRNAs in regulating cellular metabolic homeostasis, highlighting organelle-associated lncRNAs as potential clinical targets to manipulate cellular metabolism and diseases.
Subject(s)
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Citric Acid Cycle / RNA, Long Noncoding / Mitochondria Limits: Animals / Female / Humans Language: En Journal: Nat Metab Year: 2021 Document type: Article Affiliation country:
Fulltext
Add to My VHL
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Citric Acid Cycle / RNA, Long Noncoding / Mitochondria Limits: Animals / Female / Humans Language: En Journal: Nat Metab Year: 2021 Document type: Article Affiliation country: