title: Mitochondrial binding of α-enolase stabilizes mitochondrial membrane: its role in doxorubicin-induced cardiomyocyte apoptosis.
abstract: α-Enolase is a metabolic enzyme in the catabolic glycolytic pathway. In eukaryotic cells, the subcellular compartmentalization of α-enolase as well as its multifaceted functions has been identified. Here, we report that α-enolase is a regulator of cardiac mitochondria; it partially located in the mitochondria of rat cardiomyocytes. Doxorubicin treatment displaced α-enolase from mitochondria, accompanied by activation of mitochondrial cell death pathway. Furthermore, in isolated mitochondria, recombinant α-enolase significantly alleviated Ca(2+)-induced loss of membrane potential, swelling of matrix and permeabilization of membrane. In contrast, mitochondria from α-enolase knockdown H9c2 myoblasts underwent more severe membrane depolarization and swelling after Ca(2+) stimulation. In addition, α-enolase was further identified to interact with voltage dependent anion channel 1 in the outer membrane of mitochondria, which was weakened by doxorubicin. Collectively, the present study indicates that mitochondria-located α-enolase has a beneficial role in stabilizing mitochondrial membrane. In cardiomyocytes, the displacement of α-enolase from mitochondria by doxorubicin may involve in activation of the intrinsic cell death pathway.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Higher Education Mega Center, 132(#) East Wai-huan Road, Guangzhou 510006, Guangdong, PR China.
authors.forename: Si
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Higher Education Mega Center, 132(#) East Wai-huan Road, Guangzhou 510006, Guangdong, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Higher Education Mega Center, 132(#) East Wai-huan Road, Guangzhou 510006, Guangdong, PR China; Guangzhou Research Institute of Snake Venom, Guangzhou Medical College, Guangzhou 510182, Guangdong, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Higher Education Mega Center, 132(#) East Wai-huan Road, Guangzhou 510006, Guangdong, PR China.
authors.forename: Jian-tao
authors.initials: JT
authors.lastname: Ye
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Higher Education Mega Center, 132(#) East Wai-huan Road, Guangzhou 510006, Guangdong, PR China.
authors.forename: Zhi-ping
authors.initials: ZP
authors.lastname: Liu
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Higher Education Mega Center, 132(#) East Wai-huan Road, Guangzhou 510006, Guangdong, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Higher Education Mega Center, 132(#) East Wai-huan Road, Guangzhou 510006, Guangdong, PR China.
authors.forename: Xiao-yang
authors.initials: XY
authors.lastname: Huang
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Higher Education Mega Center, 132(#) East Wai-huan Road, Guangzhou 510006, Guangdong, PR China.
authors.forename: Xiao-jun
authors.initials: XJ
authors.lastname: Feng
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Higher Education Mega Center, 132(#) East Wai-huan Road, Guangzhou 510006, Guangdong, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Higher Education Mega Center, 132(#) East Wai-huan Road, Guangzhou 510006, Guangdong, PR China.
authors.forename: Shao-rui
authors.initials: SR
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Higher Education Mega Center, 132(#) East Wai-huan Road, Guangzhou 510006, Guangdong, PR China. Electronic address: limin65@mail.sysu.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Higher Education Mega Center, 132(#) East Wai-huan Road, Guangzhou 510006, Guangdong, PR China. Electronic address: liupq@mail.sysu.edu.cn.
authors.forename: Pei-qing
authors.initials: PQ
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D010751:Phosphopyruvate Hydratase / Q000378:metabolism* / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D050995:Voltage-Dependent Anion Channel 1 / Q000378:metabolism
chemical_list: D011994:Recombinant Proteins; D004317:Doxorubicin; D050995:Voltage-Dependent Anion Channel 1; D010751:Phosphopyruvate Hydratase; D002118:Calcium
keywords: Apoptosis; Cardiomyocytes; Doxorubicin; Mitochondria; Voltage dependent anion channel; α-Enolase