Mitochondrial and secretory human cytomegalovirus UL37 proteins traffic into mitochondrion-associated membranes of human cells

Journal of Virology
Petros BozidisAnamaris M Colberg-Poley

Abstract

The human cytomegalovirus (HCMV) UL37 exon 1 protein (pUL37x1), also known as vMIA, is the predominant UL37 isoform during permissive infection. pUL37x1 is a potent antiapoptotic protein, which prevents cytochrome c release from mitochondria. The UL37x1 NH(2)-terminal bipartite localization signal, which remains uncleaved, targets UL37 proteins to the endoplasmic reticulum (ER) and then to mitochondria. Based upon our findings, we hypothesized that pUL37x1 traffics from the ER to mitochondria through direct contacts between the two organelles, provided by mitochondrion-associated membranes (MAMs). To facilitate its identification, we cloned and tagged the human phosphatidylserine synthase 1 (huPSS-1) cDNA, whose mouse homologue localizes almost exclusively in the MAM. Using subcellular fractionation of stable HeLa cell transfectants expressing mEGFP-huPSS-1, we found that HCMV pUL37x1 is present in purified microsomes, mitochondria, and MAM fractions. We further examined the trafficking of the full-length UL37 glycoprotein cleavage products, which divergently traffic either through the secretory apparatus or into mitochondria. Surprisingly, pUL37(NH2) and gpUL37(COOH) were both detected in the ER and MAM fraction, even though o...Continue Reading

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Citations

Dec 24, 2010·Journal of Virology·Chad D WilliamsonAnamaris M Colberg-Poley
Sep 24, 2011·Cell Communication and Signaling : CCS·Simone PatergnaniPaolo Pinton
Jan 13, 2009·Virology Journal·Mindy Miller-Kittrell, Tim E Sparer
Apr 12, 2014·Viruses·Shivaprasad BhuvanendranAnamaris M Colberg-Poley
Aug 26, 2009·The International Journal of Biochemistry & Cell Biology·Magdalena LebiedzinskaMariusz R Wieckowski
Jun 7, 2008·Journal of Controlled Release : Official Journal of the Controlled Release Society·Elena V Batrakova, Alexander V Kabanov
Apr 16, 2009·Reviews in Medical Virology·Chad D Williamson, Anamaris M Colberg-Poley
Sep 13, 2011·Mitochondrion·Mari KaarbøLars Eide
Feb 26, 2015·Autophagy·Joanna BiazikEeva-Liisa Eskelinen
Mar 1, 2015·Medical Microbiology and Immunology·Anamaris M Colberg-PoleyJyoti K Jaiswal
May 19, 2010·Cell·Dale W HaileyJennifer Lippincott-Schwartz
Nov 7, 2019·Journal of Virology·Joseph A CombsKevin J Zwezdaryk
Aug 9, 2020·Genes·Janaina Macedo-da-SilvaLivia Rosa-Fernandes

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