Match!

Von Willebrand factor A domain-containing protein 8 (VWA8) localizes to the matrix side of the inner mitochondrial membrane

Published on Jan 1, 2020in Biochemical and Biophysical Research Communications2.705
· DOI :10.1016/j.bbrc.2019.10.095
Moulun Luo11
Estimated H-index: 11
(UA: University of Arizona),
Wuqiong Ma1
Estimated H-index: 1
(UA: University of Arizona)
+ 5 AuthorsLawrence J. Mandarino55
Estimated H-index: 55
(UA: University of Arizona)
Abstract
Abstract VWA8 is a poorly characterized mitochondrial AAA + ATPase protein. The specific submitochondrial localization of VWA8 remains unclear. The purpose of this study was to determine the specific submitochondrial compartment within which VWA8 resides in order to provide more insight into the function of this protein. Bioinformatics analysis showed that VWA8 has a 34 amino acid N-terminal Matrix-Targeting Signal (MTS) that is similar to those in proteins known to localize to the mitochondrial matrix. Experiments in C2C12 mouse myoblasts using confocal microscopy showed that deletion of the VWA8 MTS (vMTS) resulted in cytosolic, rather than mitochondrial, localization of VWA8. Biochemical analysis using differential sub-fractionation of mitochondria isolated from rat liver showed that VWA8 localizes to the matrix side of inner mitochondrial membrane, similar to the inner mitochondrial membrane protein Electron Transfer Flavoprotein-ubiquinone Oxidoreductase (ETFDH). The results of these experiments show that the vMTS is essential for localization to the mitochondrial matrix and that once there, VWA8 localizes to the matrix side of inner mitochondrial membrane.
  • References (18)
  • Citations (1)
📖 Papers frequently viewed together
76 Citations
36 Citations
98 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
References18
Newest
#1Agustin Cerani (McGill University)H-Index: 1
#2Sirui Zhou (McGill University)H-Index: 8
Last. J. Brent Richards (McGill University)H-Index: 45
view all 9 authors...
OBJECTIVE: To determine if genetically increased serum calcium levels are associated with improved bone mineral density and a reduction in osteoporotic fractures. DESIGN Mendelian randomisation stu ...
3 CitationsSource
#1Feng Yuan (HUST: Huazhong University of Science and Technology)H-Index: 1
#2Wei Wang (HUST: Huazhong University of Science and Technology)H-Index: 1
Last. Hongtao Cheng (HUST: Huazhong University of Science and Technology)H-Index: 1
view all 3 authors...
2 CitationsSource
#1Brian S. Grewe (UIC: University of Illinois at Chicago)H-Index: 1
#2Janet E. Richmond (UIC: University of Illinois at Chicago)H-Index: 34
Last. David E. Featherstone (UIC: University of Illinois at Chicago)H-Index: 26
view all 3 authors...
Abstract The Drosophila gene c12.2 was isolated in a screen examining mRNA binding proteins. Drosophila c12.2 is the mouse Vwa8 homolog. Various genome-wide associated studies have linked human Vwa8 to both neurological and oncological pathologies, which include autism, bipolar disorder, comorbid migraine, and acute myeloid leukemia, however, the function and role of the VWA8 protein remain poorly understood. To further analyze the Vwa8 gene in mouse, gene structure, protein homology modeling, a...
1 CitationsSource
#1Sandra Backes (TUK: Kaiserslautern University of Technology)H-Index: 3
#2Johannes M. Herrmann (TUK: Kaiserslautern University of Technology)H-Index: 51
Mitochondria contain two aqueous subcompartments, the matrix and the intermembrane space (IMS).The matrix is enclosed by both the inner and outer mitochondrial membranes, whilst the IMS is sandwiched between the two. Proteins of the matrix are synthesized in the cytosol as preproteins, which contain amino-terminal matrix targeting sequences that mediate their translocation through translocases embedded in the outer and inner membrane. For these proteins, the translocation reaction is driven by t...
22 CitationsSource
#1Moulun Luo (UA: University of Arizona)H-Index: 11
#2April Mengos (Mayo Clinic)H-Index: 11
Last. Lawrence J. Mandarino (UA: University of Arizona)H-Index: 55
view all 10 authors...
Abstract The VWA8 gene was first identified by the Kazusa cDNA project and named KIAA0564. Based on the observation, by similarity, that the protein encoded by KIAA0564 contains a Von Willebrand Factor 8 domain, KIAA0564 was named Von Willebrand Domain-containing Protein 8 (VWA8). The function of VWA8 protein is almost unknown. The purpose of this study was to characterize the tissue distribution, cellular location, and function of VWA8. In mice VWA8 protein was mostly distributed in liver, kidn...
4 CitationsSource
#1Joshua Strom (UA: University of Arizona)H-Index: 9
#2Beibei Xu (UA: University of Arizona)H-Index: 9
Last. Qin M. Chen (UA: University of Arizona)H-Index: 24
view all 4 authors...
Sublethal levels of oxidative stress are commonly associated with various pathophysiological conditions. Cardiomyocytes have the highest content of mitochondria among all cell types, allowing the study of mitochondria in cells surviving oxidative stress and address whether nuclear factor–erythroid-derived 2–related factor 2 (Nrf2) can reverse these changes. Mitochondria normally exist in elaborated networks, which were replaced by predominately individual punctuate mitochondria 24 h after exposu...
31 CitationsSource
#1Guido Marcucci (OSU: Ohio State University)H-Index: 83
#2Pearlly S. Yan (OSU: Ohio State University)H-Index: 47
Last. Clara D. Bloomfield (OSU: Ohio State University)H-Index: 105
view all 31 authors...
Purpose Molecular risk stratification of acute myeloid leukemia (AML) is largely based on genetic markers. However, epigenetic changes, including DNA methylation, deregulate gene expression and may also have prognostic impact. We evaluated the clinical relevance of integrating DNA methylation and genetic information in AML. Methods Next-generation sequencing analysis of methylated DNA identified differentially methylated regions (DMRs) associated with prognostic mutations in older (≥ 60 years) c...
86 CitationsSource
#1Conall M. O'Seaghdha (Harvard University)H-Index: 21
#2Hongsheng Wu (University of Split)H-Index: 5
Last. Murielle Bochud (UNIL: University of Lausanne)H-Index: 54
view all 109 authors...
Calcium is vital to the normal functioning of multiple organ systems and its serum concentration is tightly regulated. Apart from CASR, the genes associated with serum calcium are largely unknown. We conducted a genome-wide association meta-analysis of 39,400 individuals from 17 population-based cohorts and investigated the 14 most strongly associated loci in ≤ 21,679 additional individuals. Seven loci (six new regions) in association with serum calcium were identified and replicated. Rs1570669 ...
69 CitationsSource
Good fortune let me be an innocent child during World War II, a hopeful adolescent with encouraging parents during the years of German recovery, and a self-determined adult in a period of peace, freedom, and wealth. My luck continued as a scientist who could entirely follow his fancy. My mind was always set on understanding how things are made. At a certain point, I found myself confronted with the question of how mitochondria and organelles, which cannot be formed de novo, are put together. Int...
8 CitationsSource
#1Moulun Luo (ASU: Arizona State University)H-Index: 11
#2April Mengos (ASU: Arizona State University)H-Index: 11
Last. Lawrence J. Mandarino (ASU: Arizona State University)H-Index: 55
view all 4 authors...
Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, type 2 diabetes, and dyslipidemia. The purpose of this study was to identify novel proteins and pathways that contribute to the pathogenesis and complications of NAFLD. C57BL/6J male mice were fed a 60% (HFD) or 10% (LFD) high or low fat diet. HFD induced obesity, hepatic steatosis and insulin resistance (euglycemic clamps, glucose infusion rate: LFD 50.5 ± 6.4 vs. HFD 14.2 ± 9.5 μg/ (g . min); n = 12). Live...
11 CitationsSource
Cited By1
Newest
#1Tsuneo Imanaka (International University, Cambodia)H-Index: 25
#2Kosuke Kawaguchi (University of Toyama)H-Index: 9
Source