期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 52, 期 2, 页码 437-447出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2011.07.027
关键词
Cardiomyocytes; Cytoskeleton; Mitochondria; Tubulin; Regulation of respiration; Energy fluxes
资金
- INSERM
- CNRS
- Agence National de la Recherche project SYBECAR France
- Estonian Science Foundation [7823]
- Estonia Ministry of Education and Science [SF0180114Bs08]
- Austrian Science Fund (FWF) [P 22080-B20]
- National Council of Science and Technology of Mexico (CONACYT)
- Charles Auffray
- Functional Genomics and Systems Biology for Health
- Institute of Biological Sciences (Villejuif, France)
- Austrian Science Fund (FWF) [P 22080] Funding Source: researchfish
The aim of this study was to investigate the possible role of tubulin beta II, a cytoskeletal protein, in regulation of mitochondrial oxidative phosphorylation and energy fluxes in heart cells. This isotype of tubulin is closely associated with mitochondria and co-expressed with mitochondrial creatine kinase (MtCK). It can be rapidly removed by mild proteolytic treatment of permeabilized cardiomyocytes in the absence of stimulatory effect of cytochrome c, that demonstrating the intactness of the outer mitochondrial membrane. Contrary to isolated mitochondria, in permeabilized cardiomyocytes (in situ mitochondria) the addition of pyruvate kinase (PK) and phosphoenolpyruvate (PEP) in the presence of creatine had no effect on the rate of respiration controlled by activated MtCK, showing limited permeability of voltage-dependent anion channel (VDAC) in mitochondrial outer membrane (MOM) for ADP regenerated by MtCK. Under normal conditions, this effect can be considered as one of the most sensitive tests of the intactness of cardiomyocytes and controlled permeability of MOM for adenine nucleotides. However, proteolytic treatment of permeabilized cardiomyocytes with trypsin, by removing mitochondrial beta II tubulin, induces high sensitivity of MtCK-regulated respiration to PK-PEP, significantly changes its kinetics and the affinity to exogenous ADP. MtCK coupled to ATP synthasome and to VDAC controlled by tubulin beta II provides functional compartmentation of ATP in mitochondria and energy channeling into cytoplasm via phosphotransfer network. Therefore, direct transfer of mitochondrially produced ATP to sites of its utilization is largely avoided under physiological conditions, but may occur in pathology when mitochondria are damaged. This article is part of a Special Issue entitled Local Signaling in Myocytes. (C) 2011 Elsevier Ltd. All rights reserved.
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