Metabolic Characterization and Consequences of Mitochondrial Pyruvate Carrier Deficiency in <i>Drosophila melanogaster</i>
In insect, pyruvate is generally the predominant oxidative substrate for mitochondria. This metabolite is transported inside mitochondria via the mitochondrial pyruvate carrier (MPC), but whether and how this transporter controls mitochondrial oxidative capacities in insects is still relatively unkn...
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| Format: | Article |
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MDPI AG
2020-09-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/10/9/363 |
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| author | Chloé Simard Andréa Lebel Eric Pierre Allain Mohamed Touaibia Etienne Hebert-Chatelain Nicolas Pichaud |
| author_facet | Chloé Simard Andréa Lebel Eric Pierre Allain Mohamed Touaibia Etienne Hebert-Chatelain Nicolas Pichaud |
| author_sort | Chloé Simard |
| collection | DOAJ |
| description | In insect, pyruvate is generally the predominant oxidative substrate for mitochondria. This metabolite is transported inside mitochondria via the mitochondrial pyruvate carrier (MPC), but whether and how this transporter controls mitochondrial oxidative capacities in insects is still relatively unknown. Here, we characterize the importance of pyruvate transport as a metabolic control point for mitochondrial substrate oxidation in two genotypes of an insect model, <i>Drosophila melanogaster</i>, differently expressing MPC1, an essential protein for the MPC function. We evaluated the kinetics of pyruvate oxidation, mitochondrial oxygen consumption, metabolic profile, activities of metabolic enzymes, and climbing abilities of wild-type (WT) flies and flies harboring a deficiency in MPC1 (MPC1<sup>def</sup>). We hypothesized that MPC1 deficiency would cause a metabolic reprogramming that would favor the oxidation of alternative substrates. Our results show that the MPC1<sup>def</sup> flies display significantly reduced climbing capacity, pyruvate-induced oxygen consumption, and enzymatic activities of pyruvate kinase, alanine aminotransferase, and citrate synthase. Moreover, increased proline oxidation capacity was detected in MPC1<sup>def</sup> flies, which was associated with generally lower levels of several metabolites, and particularly those involved in amino acid catabolism such as ornithine, citrulline, and arginosuccinate. This study therefore reveals the flexibility of mitochondrial substrate oxidation allowing Drosophila to maintain cellular homeostasis. |
| first_indexed | 2024-03-10T16:31:47Z |
| format | Article |
| id | doaj.art-4693dc03950c4483ab81580a7cc109d8 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T16:31:47Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-4693dc03950c4483ab81580a7cc109d82023-11-20T12:45:37ZengMDPI AGMetabolites2218-19892020-09-0110936310.3390/metabo10090363Metabolic Characterization and Consequences of Mitochondrial Pyruvate Carrier Deficiency in <i>Drosophila melanogaster</i>Chloé Simard0Andréa Lebel1Eric Pierre Allain2Mohamed Touaibia3Etienne Hebert-Chatelain4Nicolas Pichaud5Department of Chemistry and Biochemistry, Université de Moncton, Moncton, NB E1A 3E9, CanadaDepartment of Chemistry and Biochemistry, Université de Moncton, Moncton, NB E1A 3E9, CanadaAtlantic Cancer Research Institute (ACRI), Moncton, NB E1C 8X3, CanadaDepartment of Chemistry and Biochemistry, Université de Moncton, Moncton, NB E1A 3E9, CanadaDepartment of Biology, Université de Moncton, Moncton, NB E1A 3E9, CanadaDepartment of Chemistry and Biochemistry, Université de Moncton, Moncton, NB E1A 3E9, CanadaIn insect, pyruvate is generally the predominant oxidative substrate for mitochondria. This metabolite is transported inside mitochondria via the mitochondrial pyruvate carrier (MPC), but whether and how this transporter controls mitochondrial oxidative capacities in insects is still relatively unknown. Here, we characterize the importance of pyruvate transport as a metabolic control point for mitochondrial substrate oxidation in two genotypes of an insect model, <i>Drosophila melanogaster</i>, differently expressing MPC1, an essential protein for the MPC function. We evaluated the kinetics of pyruvate oxidation, mitochondrial oxygen consumption, metabolic profile, activities of metabolic enzymes, and climbing abilities of wild-type (WT) flies and flies harboring a deficiency in MPC1 (MPC1<sup>def</sup>). We hypothesized that MPC1 deficiency would cause a metabolic reprogramming that would favor the oxidation of alternative substrates. Our results show that the MPC1<sup>def</sup> flies display significantly reduced climbing capacity, pyruvate-induced oxygen consumption, and enzymatic activities of pyruvate kinase, alanine aminotransferase, and citrate synthase. Moreover, increased proline oxidation capacity was detected in MPC1<sup>def</sup> flies, which was associated with generally lower levels of several metabolites, and particularly those involved in amino acid catabolism such as ornithine, citrulline, and arginosuccinate. This study therefore reveals the flexibility of mitochondrial substrate oxidation allowing Drosophila to maintain cellular homeostasis.https://www.mdpi.com/2218-1989/10/9/363drosophilakineticsmetabolomicsmitochondrial pyruvate carriermitochondrial respiration |
| spellingShingle | Chloé Simard Andréa Lebel Eric Pierre Allain Mohamed Touaibia Etienne Hebert-Chatelain Nicolas Pichaud Metabolic Characterization and Consequences of Mitochondrial Pyruvate Carrier Deficiency in <i>Drosophila melanogaster</i> Metabolites drosophila kinetics metabolomics mitochondrial pyruvate carrier mitochondrial respiration |
| title | Metabolic Characterization and Consequences of Mitochondrial Pyruvate Carrier Deficiency in <i>Drosophila melanogaster</i> |
| title_full | Metabolic Characterization and Consequences of Mitochondrial Pyruvate Carrier Deficiency in <i>Drosophila melanogaster</i> |
| title_fullStr | Metabolic Characterization and Consequences of Mitochondrial Pyruvate Carrier Deficiency in <i>Drosophila melanogaster</i> |
| title_full_unstemmed | Metabolic Characterization and Consequences of Mitochondrial Pyruvate Carrier Deficiency in <i>Drosophila melanogaster</i> |
| title_short | Metabolic Characterization and Consequences of Mitochondrial Pyruvate Carrier Deficiency in <i>Drosophila melanogaster</i> |
| title_sort | metabolic characterization and consequences of mitochondrial pyruvate carrier deficiency in i drosophila melanogaster i |
| topic | drosophila kinetics metabolomics mitochondrial pyruvate carrier mitochondrial respiration |
| url | https://www.mdpi.com/2218-1989/10/9/363 |
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