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Nutrition controls mitochondrial biogenesis in the Drosophila adipose tissue through Delg and cyclin D/Cdk4.

Baltzer C, Tiefenböck SK, Marti M, Frei C - PLoS ONE (2009)

Bottom Line: This correlates with reduced expression of genes encoding mitochondrial proteins, particularly genes involved in oxidative phosphorylation.However, in contrast to nutrients, Delg is not involved in the regulation of mitochondrial activity in the fat body.These findings are the first genetic evidence that the regulation of mitochondrial mass can be uncoupled from mitochondrial activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, ETH Zurich, Zurich, Switzerland.

ABSTRACT
MITOCHONDRIA ARE CELLULAR ORGANELLES THAT PERFORM CRITICAL METABOLIC FUNCTIONS: they generate energy from nutrients but also provide metabolites for de novo synthesis of fatty acids and several amino acids. Thus mitochondrial mass and activity must be coordinated with nutrient availability, yet this remains poorly understood. Here, we demonstrate that Drosophila larvae grown in low yeast food have strong defects in mitochondrial abundance and respiration activity in the larval fat body. This correlates with reduced expression of genes encoding mitochondrial proteins, particularly genes involved in oxidative phosphorylation. Second, genes involved in glutamine metabolism are also expressed in a nutrient-dependent manner, suggesting a coordination of amino acid synthesis with mitochondrial abundance and activity. Moreover, we show that Delg (CG6338), the Drosophila homologue to the alpha subunit of mammalian transcription factor NRF-2/GABP, is required for proper expression of most genes encoding mitochondrial proteins. Our data demonstrate that Delg is critical to adjust mitochondrial abundance in respect to Cyclin D/Cdk4, a growth-promoting complex and glutamine metabolism according to nutrient availability. However, in contrast to nutrients, Delg is not involved in the regulation of mitochondrial activity in the fat body. These findings are the first genetic evidence that the regulation of mitochondrial mass can be uncoupled from mitochondrial activity.

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Expression levels in the fat body and the gut of candidate transcription factors to control the expression of genes encoding mitochondrial proteins.The larval fat body or gut was dissected from mid-third instar larvae (4d AED for +/Df(3R)ro80b, and 6d AED for delg613/Df(3R)ro80b), and mRNA levels were determined using qPCR and normalized to Tubulin levels. (A) Drosophila homologues to mammalian NRF-2α are shown. (B) dMyc, Estrogen-related receptor (ERR) and Spargel (Drosophila PGC-1 homologue) levels are shown. Significance between the fat body and the gut for control animals is shown below the charts, and significance between control and delg mutant is shown within the charts.
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pone-0006935-g003: Expression levels in the fat body and the gut of candidate transcription factors to control the expression of genes encoding mitochondrial proteins.The larval fat body or gut was dissected from mid-third instar larvae (4d AED for +/Df(3R)ro80b, and 6d AED for delg613/Df(3R)ro80b), and mRNA levels were determined using qPCR and normalized to Tubulin levels. (A) Drosophila homologues to mammalian NRF-2α are shown. (B) dMyc, Estrogen-related receptor (ERR) and Spargel (Drosophila PGC-1 homologue) levels are shown. Significance between the fat body and the gut for control animals is shown below the charts, and significance between control and delg mutant is shown within the charts.

Mentions: Even in a delg mutant background, mitochondria are still present in the larval fat body. Moreover, Delg is expressed in the larval gut to similar levels as in the fat body (data not shown), yet we did not observe mitochondrial phenotypes in delg mutants (Fig. S2). Thus redundant factors, especially in the gut, must exist. To identify such factors, we dissected larval fat bodies and guts from mid-third instar animals, either control or delg mutant. qPCR was then used to measure mRNA levels of the Drosophila NRF-2α homologues mentioned above. Three of them, Ets21C, Pointed and Aop, were expressed at higher levels in the gut, compared to the fat body, thus potentially explaining the absence of phenotypes in delg mutant gut cells. Moreover, Ets96B was expressed at higher levels in the delg mutant fat body, compared to the control fat body (Fig. 3A). A detailed genetic characterization including double mutants between Delg and other NRF-2α homologues will be required to directly test for redundancy.


Nutrition controls mitochondrial biogenesis in the Drosophila adipose tissue through Delg and cyclin D/Cdk4.

Baltzer C, Tiefenböck SK, Marti M, Frei C - PLoS ONE (2009)

Expression levels in the fat body and the gut of candidate transcription factors to control the expression of genes encoding mitochondrial proteins.The larval fat body or gut was dissected from mid-third instar larvae (4d AED for +/Df(3R)ro80b, and 6d AED for delg613/Df(3R)ro80b), and mRNA levels were determined using qPCR and normalized to Tubulin levels. (A) Drosophila homologues to mammalian NRF-2α are shown. (B) dMyc, Estrogen-related receptor (ERR) and Spargel (Drosophila PGC-1 homologue) levels are shown. Significance between the fat body and the gut for control animals is shown below the charts, and significance between control and delg mutant is shown within the charts.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2735006&req=5

pone-0006935-g003: Expression levels in the fat body and the gut of candidate transcription factors to control the expression of genes encoding mitochondrial proteins.The larval fat body or gut was dissected from mid-third instar larvae (4d AED for +/Df(3R)ro80b, and 6d AED for delg613/Df(3R)ro80b), and mRNA levels were determined using qPCR and normalized to Tubulin levels. (A) Drosophila homologues to mammalian NRF-2α are shown. (B) dMyc, Estrogen-related receptor (ERR) and Spargel (Drosophila PGC-1 homologue) levels are shown. Significance between the fat body and the gut for control animals is shown below the charts, and significance between control and delg mutant is shown within the charts.
Mentions: Even in a delg mutant background, mitochondria are still present in the larval fat body. Moreover, Delg is expressed in the larval gut to similar levels as in the fat body (data not shown), yet we did not observe mitochondrial phenotypes in delg mutants (Fig. S2). Thus redundant factors, especially in the gut, must exist. To identify such factors, we dissected larval fat bodies and guts from mid-third instar animals, either control or delg mutant. qPCR was then used to measure mRNA levels of the Drosophila NRF-2α homologues mentioned above. Three of them, Ets21C, Pointed and Aop, were expressed at higher levels in the gut, compared to the fat body, thus potentially explaining the absence of phenotypes in delg mutant gut cells. Moreover, Ets96B was expressed at higher levels in the delg mutant fat body, compared to the control fat body (Fig. 3A). A detailed genetic characterization including double mutants between Delg and other NRF-2α homologues will be required to directly test for redundancy.

Bottom Line: This correlates with reduced expression of genes encoding mitochondrial proteins, particularly genes involved in oxidative phosphorylation.However, in contrast to nutrients, Delg is not involved in the regulation of mitochondrial activity in the fat body.These findings are the first genetic evidence that the regulation of mitochondrial mass can be uncoupled from mitochondrial activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, ETH Zurich, Zurich, Switzerland.

ABSTRACT
MITOCHONDRIA ARE CELLULAR ORGANELLES THAT PERFORM CRITICAL METABOLIC FUNCTIONS: they generate energy from nutrients but also provide metabolites for de novo synthesis of fatty acids and several amino acids. Thus mitochondrial mass and activity must be coordinated with nutrient availability, yet this remains poorly understood. Here, we demonstrate that Drosophila larvae grown in low yeast food have strong defects in mitochondrial abundance and respiration activity in the larval fat body. This correlates with reduced expression of genes encoding mitochondrial proteins, particularly genes involved in oxidative phosphorylation. Second, genes involved in glutamine metabolism are also expressed in a nutrient-dependent manner, suggesting a coordination of amino acid synthesis with mitochondrial abundance and activity. Moreover, we show that Delg (CG6338), the Drosophila homologue to the alpha subunit of mammalian transcription factor NRF-2/GABP, is required for proper expression of most genes encoding mitochondrial proteins. Our data demonstrate that Delg is critical to adjust mitochondrial abundance in respect to Cyclin D/Cdk4, a growth-promoting complex and glutamine metabolism according to nutrient availability. However, in contrast to nutrients, Delg is not involved in the regulation of mitochondrial activity in the fat body. These findings are the first genetic evidence that the regulation of mitochondrial mass can be uncoupled from mitochondrial activity.

Show MeSH