Sequence and tissue-dependent RNA expression of mouse FAD-linked glycerol-3-phosphate dehydrogenase
Abstract
A 2432-bp cDNA for mouse FAD-linked glycerol-3-phosphate dehydrogenase, a nuclear-encoded enzyme associated with the inner mitochondrial membrane, was isolated from a Lambda ZAP phage library generated from brown adipocyte mRNA. The amino acid sequence was 95 and 93% homologous to the rat and human enzymes. PvuII and SacI polymorphisms between Mus spretus and C57BL/6J were used to map the mouse FAD-linked glycerol-3-phosphate dehydrogenase gene (Gdm1) to chromosome 2, 33 cM from the centromere. Northern blot analysis showed that brown adipose tissue predominantly expressed a 6.5-kb mRNA with lower expression of 4.5- and 2.4-kb forms, whereas brain and pancreatic islets almost exclusively expressed a 6.5-kb transcript, muscle expressed a 4.5-kb transcript, and testis expressed a 2.4-kb RNA form. Analysis of poly(A)+ RNA from brown adipose tissue suggested that all RNA forms are polyadenylated. Among the tissues examined, FAD-linked glycerol-3-phosphate dehydrogenase protein levels and enzyme activity were highest in brown adipose tissue, and a consistent correlation between protein levels and enzyme activity in all tissues was observed. RNA levels corresponded to protein levels in all tissues except testis, where high levels of 2.4-kb mRNA and relatively low protein were expressed. Exposing mice to cold temperatures induced the 6.5-kb mRNA and enzyme activity only in brown adipose tissue, suggesting a role for thermogenesis in this tissue. Although the molecular basis for the formation of the 6.5- and 4.5-kb mRNA's is not known, data suggest that the regulation of FAD-linked glycerol-3-phosphate dehydrogenase is complex and tissue-specific.
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The glycerol 3-phosphate shuttle is not considered the major route of NADH shuttling in most mammalian cells but is particularly active in brown adipose tissue and may be implicated in thermoregulation.
“The glycerol 3-phosphate shuttle is not considered the major route of NADH shuttling in most mammalian cells but has been shown to be particularly active in brown adipose tissue and may be implicated in thermoregulation (105, 106, 107).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [105]
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- Authors
- Koza, R. A., Kozak, U. C., Brown, L. J., Leiter, E. H., Macdonald, M. J., & Kozak, L. P.
- Affiliations
- Jackson Laboratory (US)
- University of Wisconsin–Madison (US)
- Corresponding author
- Kozak, L.P.
- Venue
- Archives of Biochemistry and Biophysics
- Publisher
- Elsevier BV
- Published
- 1996-12
- Volume
- 336
- Issue
- 1
- Pages
- 97-104
- ISSN
- 0003-9861 (ISSN-L)
- OpenAlex
- W1976399147
- Cited by
- 76
- References
- 0
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 1 · 2015: 5 · 2014: 2 · 2013: 1 · 2012: 4
- FWCI
- 0.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Biochemistry and Biophysics (publishedVersion)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- National Institutes of Health (1r01hd029149-01a1)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK036175, DK 28348, DK-36175)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-29149)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- mice, cDNA cloning, gene mapping, brown adipose tissue, tissue-specific gene expression, mRNA isoforms, cold-induced thermogenesis, inner mitochondrial membrane, polyadenylation, enzyme activity, Mus spretus, C57BL/6J mice
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Binding Sites, Adipose Tissue, Brown, Chromosome Mapping, Cloning, Molecular, Cold Temperature, Flavin-Adenine Dinucleotide, Glycerolphosphate Dehydrogenase, Humans, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria, Molecular Sequence Data, Regulatory Sequences, Nucleic Acid, Tissue Distribution, Gene Expression Regulation, Enzymologic, Mice, Rats
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