Ethanolamine ameliorates mitochondrial dysfunction in cardiolipin-deficient yeast cells.

Autor:	Basu Ball W; From the Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843., Baker CD; From the Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843., Neff JK; From the Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843., Apfel GL; From the Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843., Lagerborg KA; the Departments of Medicine and Pharmacology, University of California, San Diego, La Jolla, California 92093., Žun G; the Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Jamova 39, Ljubljana, Slovenia.; the Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, 1000 Ljubljana, Slovenia, and., Petrovič U; the Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Jamova 39, Ljubljana, Slovenia.; the Department of Biology, Biotechnical Faculty, University of Ljubljana, Večna pot 111, 1000 Ljubljana, Slovenia., Jain M; the Departments of Medicine and Pharmacology, University of California, San Diego, La Jolla, California 92093., Gohil VM; From the Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843, vgohil@tamu.edu.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2018 Jul 13; Vol. 293 (28), pp. 10870-10883. Date of Electronic Publication: 2018 Jun 04.
DOI:	10.1074/jbc.RA118.004014
Abstrakt:	Cardiolipin (CL) is a signature phospholipid of the mitochondria required for the formation of mitochondrial respiratory chain (MRC) supercomplexes. The destabilization of MRC supercomplexes is the proximal cause of the pathology associated with the depletion of CL in patients with Barth syndrome. Thus, promoting supercomplex formation could ameliorate mitochondrial dysfunction associated with CL depletion. However, to date, physiologically relevant small-molecule regulators of supercomplex formation have not been identified. Here, we report that ethanolamine (Etn) supplementation rescues the MRC defects by promoting supercomplex assembly in a yeast model of Barth syndrome. We discovered this novel role of Etn while testing the hypothesis that elevating mitochondrial phosphatidylethanolamine (PE), a phospholipid suggested to overlap in function with CL, could compensate for CL deficiency. We found that the Etn supplementation rescues the respiratory growth of CL-deficient Saccharomyces cerevisiae cells in a dose-dependent manner but independently of its incorporation into PE. The rescue was specifically dependent on Etn but not choline or serine, the other phospholipid precursors. Etn improved mitochondrial function by restoring the expression of MRC proteins and promoting supercomplex assembly in CL-deficient cells. Consistent with this mechanism, overexpression of Cox4, the MRC complex IV subunit, was sufficient to promote supercomplex formation in CL-deficient cells. Taken together, our work identifies a novel role of a ubiquitous metabolite, Etn, in attenuating mitochondrial dysfunction caused by CL deficiency. (© 2018 Basu Ball et al.)
Databáze:	MEDLINE
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