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      Interaction of Mitochondria with the Endoplasmic Reticulum and Plasma Membrane in Calcium Homeostasis, Lipid Trafficking and Mitochondrial Structure

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          Abstract

          Studying organelles in isolation has been proven to be indispensable for deciphering the underlying mechanisms of molecular cell biology. However, observing organelles in intact cells with the use of microscopic techniques reveals a new set of different junctions and contact sites between them that contribute to the control and regulation of various cellular processes, such as calcium and lipid exchange or structural reorganization of the mitochondrial network. In recent years, many studies focused their attention on the structure and function of contacts between mitochondria and other organelles. From these studies, findings emerged showing that these contacts are involved in various processes, such as lipid synthesis and trafficking, modulation of mitochondrial morphology, endoplasmic reticulum (ER) stress, apoptosis, autophagy, inflammation and Ca 2 + handling. In this review, we focused on the physical interactions of mitochondria with the endoplasmic reticulum and plasma membrane and summarized present knowledge regarding the role of mitochondria-associated membranes in calcium homeostasis and lipid metabolism.

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          Most cited references107

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          An ER-mitochondria tethering complex revealed by a synthetic biology screen.

          Communication between organelles is an important feature of all eukaryotic cells. To uncover components involved in mitochondria/endoplasmic reticulum (ER) junctions, we screened for mutants that could be complemented by a synthetic protein designed to artificially tether the two organelles. We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. The tethering complex was composed of proteins resident of both ER and mitochondria. With the use of genome-wide mapping of genetic interactions, we showed that the components of the tethering complex were functionally connected to phospholipid biosynthesis and calcium-signaling genes. In mutant cells, phospholipid biosynthesis was impaired. The tethering complex localized to discrete foci, suggesting that discrete sites of close apposition between ER and mitochondria facilitate interorganelle calcium and phospholipid exchange.
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            Phospholipid synthesis in a membrane fraction associated with mitochondria.

            J Vance (1990)
            A crude rat liver mitochondrial fraction that was capable of the rapid, linked synthesis of phosphatidylserine (PtdSer), phosphatidylethanolamine (PtdEtn), and phosphatidylcholine (PtdCho) labeled from [3-3H] serine has been fractionated. PtdSer synthase, PtdEtn methyltransferase, and CDP-choline:diacylglycerol cholinephosphotransferase activities were present in the crude mitochondrial preparation but were absent from highly purified mitochondria and could be attributed to the presence of a membrane fraction, X. Thus, previous claims of the mitochondrial location of some of these enzymes might be explained by the presence of fraction X in the mitochondrial preparation. Fraction X had many similarities to microsomes except that it sedimented with mitochondria (at 10,000 x g). However, the specific activities of PtdSer synthase and glucose-6-phosphate phosphatase in fraction X were almost twice that of microsomes, and the specific activities of CTP:phosphocholine cytidylyltransferase and NADPH:cytochrome c reductase in fraction X were much lower than in microsomes. The marker enzymes for mitochondria, Golgi apparatus, plasma membrane, lysosomes, and peroxisomes all had low activities in fraction X. Polyacrylamide gel electrophoresis revealed distinct differences, as well as similarities, among the proteins of fraction X, microsomes, and rough and smooth endoplasmic reticulum. The combined mitochondria-fraction X membranes can synthesize PtdSer, PtdEtn, and PtdCho from serine. Thus, fraction X in combination with mitochondria might be responsible for the observed compartmentalization of a serine-labeled pool of phospholipids previously identified (Vance, J. E., and Vance, D. E. (1986) J. Biol. Chem. 261, 4486-4491) and might be involved in the transfer of lipids between the endoplasmic reticulum and mitochondria.
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              From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS.

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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                20 July 2017
                July 2017
                : 18
                : 7
                : 1576
                Affiliations
                [1 ]Department of Biochemistry, Nencki Institute of Experimental Biology, Pasteur 3, 02-093 Warsaw, Poland; j.szymanski@ 123456nencki.gov.pl (J.S.); j.janikiewicz@ 123456nencki.gov.pl (J.J.); b.michalska@ 123456nencki.gov.pl (B.M.); p.patalas@ 123456nencki.gov.pl (P.P.-K.); j.duszynski@ 123456nencki.gov.pl (J.D.); a.dobrzyn@ 123456nencki.gov.pl (A.D.)
                [2 ]Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 44121 Ferrara, Italy; prrmsl@ 123456unife.it (M.P.); paolo.pinton@ 123456unife.it (P.P.)
                [3 ]Department of Bioenergetics and Nutrition, Gdańsk University of Physical Education and Sport, 80-336 Gdańsk, Poland; wiech@ 123456awf.gda.pl
                Author notes
                [* ]Correspondence: m.wieckowski@ 123456nencki.gov.pl ; Tel.: +48-22-589-23-72; Fax: +48-22-822-53-42
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-4060-0196
                https://orcid.org/0000-0001-7108-6508
                Article
                ijms-18-01576
                10.3390/ijms18071576
                5536064
                28726733
                c55b169c-6fad-47d1-b002-3fbd977efb58
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 May 2017
                : 13 July 2017
                Categories
                Review

                Molecular biology
                mitochondria,endoplasmic reticulum,plasma membrane,mitochondria-associated membranes (mam),plasma membrane-associated membranes (pam),lipid metabolism and trafficking

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