Linked Life Data

12759376

Source:http://linkedlifedata.com/resource/pubmed/id/12759376

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 13
pubmed:dateCreated
2003-5-30
pubmed:abstractText
Mitochondrial fusion may regulate mitochondrial morphogenesis and underlie complementation between mitochondrial genomes in mammalian cells. The nuclear encoded mitochondrial proteins Mfn1 and Mfn2 are human homologues of the only known protein mediators of mitochondrial fusion, the Drosophila Fzo GTPase and Saccharomyces cerevisiae yFzo1p. Although the Mfn1 and Mfn2 genes were broadly expressed, the two genes showed different levels of mRNA expression in different tissues. Two Mfn1 transcripts were detected at similar levels in a variety of human tissues and were dramatically elevated in heart, while Mfn2 mRNA was abundantly expressed in heart and muscle tissue but present only at low levels in many other tissues. Human Mfn1 protein localized to mitochondria and participated in a high molecular weight, detergent extractable protein complex. Forced expression of Mfn1 in cultured cells caused formation of characteristic networks of mitochondria. Introduction of a point mutation in the conserved G1 region of the predicted GTPase domain (Mfn1K88T) dramatically decreased formation of mitochondrial networks upon Mfn1 overexpression, suggesting that network formation required completion of the Mfn1 GTPase cycle. Conversely, a protein variant carrying a point mutation in the G2 motif of the Mfn1 GTPase domain acted as a dominant negative: overexpression of Mfn1T109A resulted in fragmentation of mitochondria. We propose that Mfn1T109A interferes with fusion activity of endogenous Mfn1 protein, possibly by binding necessary cofactors, so to allow unopposed mitochondrial fission. Thus, Mfn1 appears to be a key player in mediating mitochondrial fusion and morphology in mammalian cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
116
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2763-74
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:12759376-Animals, pubmed-meshheading:12759376-COS Cells, pubmed-meshheading:12759376-Drosophila Proteins, pubmed-meshheading:12759376-Energy Metabolism, pubmed-meshheading:12759376-GTP Phosphohydrolases, pubmed-meshheading:12759376-Gene Expression Regulation, pubmed-meshheading:12759376-Intracellular Membranes, pubmed-meshheading:12759376-Mammals, pubmed-meshheading:12759376-Membrane Fusion, pubmed-meshheading:12759376-Membrane Proteins, pubmed-meshheading:12759376-Membrane Transport Proteins, pubmed-meshheading:12759376-Microscopy, Electron, pubmed-meshheading:12759376-Mitochondria, pubmed-meshheading:12759376-Mitochondrial Membrane Transport Proteins, pubmed-meshheading:12759376-Mitochondrial Proteins, pubmed-meshheading:12759376-Molecular Sequence Data, pubmed-meshheading:12759376-Mutation, pubmed-meshheading:12759376-Protein Structure, Tertiary, pubmed-meshheading:12759376-RNA, Messenger, pubmed-meshheading:12759376-Sequence Homology, Amino Acid, pubmed-meshheading:12759376-Sequence Homology, Nucleic Acid
pubmed:year
2003
pubmed:articleTitle
Mitofusin-1 protein is a generally expressed mediator of mitochondrial fusion in mammalian cells.
pubmed:affiliation
Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't