Mimivirus-Encoded Nucleotide Translocator VMC1 Targets the Mitochondrial Inner Membrane. Issue 24 (7th December 2018)

• Record Type: Journal Article
• Authors: Zara, Vincenzo; Ferramosca, Alessandra; Günnewig, Kathrin; Kreimendahl, Sebastian; Schwichtenberg, Jan; Sträter, Dina; Çakar, Mahmut; Emmrich, Kerstin; Guidato, Patrick; Palmieri, Ferdinando; Rassow, Joachim
• Is Part Of: Journal of molecular biology. Volume 430:Issue 24(2018)
• Page Start: 5233
• Page End: 5245
• Publication Date: 2018-12-07
• Subjects: AAC ADP/ATP carrier -- CCCP carbonyl cyanide m-chlorophenylhydrazone -- DCFH-DA 2′, 7′-dichlorodihydrofluorescein diacetate -- DHFR dihydrofolate reductase -- MCF mitochondrial carrier family -- NEM N-ethylmaleimide -- TIM translocase of the mitochondrial inner membrane -- TOM translocase of the mitochondrial outer membrane -- VMC1 viral mitochondrial carrier 1; mimivirus -- VMC1 -- mitochondrial carrier family -- mitochondria -- Tom40; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2018.09.012
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: Mimivirus ( Acanthamoeba polyphaga mimivirus) was the first giant DNA virus identified in an amoeba species. Its genome contains at least 979 genes. One of these, L276, encodes a nucleotide translocator with similarities to mitochondrial metabolite carriers, provisionally named viral mitochondrial carrier 1 (VMC1). In this study, we investigated the intracellular distribution of VMC1 upon expression in HeLa cells and in the yeast Saccharomyces cerevisiae . We found that VMC1 is specifically targeted to mitochondria and to the inner mitochondrial membrane. Newly synthesized VMC1 binds to the mitochondrial outer-membrane protein Tom70 and translocates through the import channel formed by the β-barrel protein Tom40. Derivatization of the four cysteine residues inside Tom40 by N -ethylmaleimide caused a delay in translocation but not a complete occlusion. Cell viability was not reduced by VMC1. Neither the mitochondrial membrane potential nor the intracellular production of reactive oxygen species was affected. Similar to endogenous metabolite carriers, mimivirus-encoded VMC1 appears to act as a specific translocator in the mitochondrial inner membrane. Due to its permeability for deoxyribonucleotides, VMC1 confers to the mitochondria an opportunity to contribute nucleotides for the replication of the large DNA genome of the virus. Graphical Abstract: Highlights: Data are presented on VMC1, a nucleotide carrier encoded by gene L276 of Mimivirus, a giant DNA virus. VMC1 is shown to target the mitochondrial inner membrane. Translocation into the mitochondria is mediated by the mitochondrial outer-membrane protein Tom40. Import of VMC1 into the mitochondria continues after partial occlusion of the import channel. VMC1 is suggested to pass through the narrow import channel in an extended conformation.