title: GABP transcription factor (nuclear respiratory factor 2) is required for mitochondrial biogenesis.
abstract: Mitochondria are membrane-bound cytoplasmic organelles that serve as the major source of ATP production in eukaryotic cells. GABP (also known as nuclear respiratory factor 2) is a nuclear E26 transformation-specific transcription factor (ETS) that binds and activates mitochondrial genes that are required for electron transport and oxidative phosphorylation. We conditionally deleted Gabpa, the DNA-binding component of this transcription factor complex, from mouse embryonic fibroblasts (MEFs) to examine the role of Gabp in mitochondrial biogenesis, function, and gene expression. Gabpα loss modestly reduced mitochondrial mass, ATP production, oxygen consumption, and mitochondrial protein synthesis but did not alter mitochondrial morphology, membrane potential, apoptosis, or the expression of several genes that were previously reported to be GABP targets. However, the expression of Tfb1m, a methyltransferase that modifies ribosomal rRNA and is required for mitochondrial protein translation, was markedly reduced in Gabpα-null MEFs. We conclude that Gabp regulates Tfb1m expression and plays an essential, nonredundant role in mitochondrial biogenesis.
authors: University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors: Zhong-Fa
authors: ZF
authors: Yang
authors: Rambam Medical Center, Haifa, Israel.
authors: Karen
authors: K
authors: Drumea
authors: Brown University, Rhode Island Hospital, Providence, Rhode Island, USA.
authors: Stephanie
authors: S
authors: Mott
authors: University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors: Junling
authors: J
authors: Wang
authors: University of Massachusetts Medical School, Worcester, Massachusetts, USA Alan.Rosmarin@umassmed.edu.
authors: Alan G
authors: AG
authors: Rosmarin
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D051268:GA-Binding Protein Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D050259:Genes, Mitochondrial; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism*; D010101:Oxygen Consumption; D012335:RNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D051268:GA-Binding Protein Transcription Factor; C495656:Gabpa protein, mouse; D012335:RNA, Ribosomal; C462441:Tfb1m protein, mouse; D014157:Transcription Factors; D000255:Adenosine Triphosphate