气候变化领域集成服务门户(CCPortal): Selective autophagy of AKAP11 activates cAMP/PKA to fuel mitochondrial metabolism and tumor cell growth

CCPortal

DOI	10.1073/pnas.2020215118
	Selective autophagy of AKAP11 activates cAMP/PKA to fuel mitochondrial metabolism and tumor cell growth
	Deng Z.; Li X.; Ramirez M.B.; Purtell K.; Choi I.; Lu J.-H.; Yu Q.; Yue Z.
发表日期	2021
ISSN	00278424
卷号	118 期号:14
英文摘要	Autophagy is a catabolic pathway that provides self-nourishment and maintenance of cellular homeostasis. Autophagy is a fundamental cell protection pathway through metabolic recycling of various intracellular cargos and supplying the breakdown products. Here, we report an autophagy function in governing cell protection during cellular response to energy crisis through cell metabolic rewiring. We observe a role of selective type of autophagy in direct activation of cyclic AMP protein kinase A (PKA) and rejuvenation of mitochondrial function. Mechanistically, autophagy selectively degrades the inhibitory subunit RI of PKA holoenzyme through A-kinase-anchoring protein (AKAP) 11. AKAP11 acts as an autophagy receptor that recruits RI to autophagosomes via LC3. Glucose starvation induces AKAP11-dependent degradation of RI, resulting in PKA activation that potentiates PKA-cAMP response element-binding signaling, mitochondria respiration, and ATP production in accordance with mitochondrial elongation. AKAP11 deficiency inhibits PKA activation and impairs cell survival upon glucose starvation. Our results thus expand the view of autophagy cytoprotection mechanism by demonstrating selective autophagy in RI degradation and PKA activation that fuels the mitochondrial metabolism and confers cell resistance to glucose deprivation implicated in tumor growth. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	AKAP11; Autophagy; Cell survival; Mitochondrial metabolism; PKA
语种	英语
scopus关键词	autophagy related protein; cyclic AMP dependent protein kinase; cyclic AMP dependent protein kinase anchoring protein; holoenzyme; protein LC3; unclassified drug; animal cell; animal tissue; Article; autophagosome; autophagy (cellular); cell activation; cell culture; cell death; cell elongation; cell function; cell protection; cell selection; cell survival; cell viability; cell viability assay; colony formation; controlled study; electron microscopy; enzyme activation; enzyme activity; enzyme synthesis; fluorescence microscopy; glucose metabolism; human; human cell; immunoblotting; immunoprecipitation; in vitro study; metabolic stress; mitochondrial respiration; mouse; nonhuman; priority journal; protein degradation; protein function; protein phosphorylation; protein purification; real time polymerase chain reaction; rejuvenation; signal transduction; tumor growth
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180003
作者单位	Department of Neurology, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; Department of Neuroscience, The Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States; State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, 999078, Macau; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
推荐引用方式 GB/T 7714	Deng Z.,Li X.,Ramirez M.B.,et al. Selective autophagy of AKAP11 activates cAMP/PKA to fuel mitochondrial metabolism and tumor cell growth[J],2021,118(14).
APA	Deng Z..,Li X..,Ramirez M.B..,Purtell K..,Choi I..,...&Yue Z..(2021).Selective autophagy of AKAP11 activates cAMP/PKA to fuel mitochondrial metabolism and tumor cell growth.Proceedings of the National Academy of Sciences of the United States of America,118(14).
MLA	Deng Z.,et al."Selective autophagy of AKAP11 activates cAMP/PKA to fuel mitochondrial metabolism and tumor cell growth".Proceedings of the National Academy of Sciences of the United States of America 118.14(2021).